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Sanjaya Kuruppu
School of Biomedical Sciences, University of Queensland, Brisbane, Australia

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Research article
Published: 30 October 2020 in Clinical Science
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Heart failure (HF) is associated with impaired L-arginine transport. In the present study, we tested the hypothesis that augmented L-arginine transport prevents the loss of kidney function in HF. Renal function was assessed in wildtype mice (WT), transgenic mice with HF (dilated cardiomyopathy, DCM) and double transgenic mice (double transgenic mice with DCM and CAT-1 overexpression, HFCAT-1) with HF and endothelial-specific overexpression of the predominant L-arginine transporter, cationic amino acid transporter-1 (CAT-1) (n=4-8/group). Cardiac function was assessed via echocardiography and left ventricular catheterisation. Renal function was assessed via quantification of albuminuria and creatinine clearance. Plasma nitrate and nitrite levels together with renal fibrosis and inflammatory markers were also quantified at study end. Albumin/creatinine ratio was two-fold greater in DCM mice than in WT mice (P=0.002), and tubulointerstitial and glomerular fibrosis were approximately eight- and three-fold greater, respectively, in DCM mice than in WT mice (P≤0.02). Critically, urinary albumin/creatinine ratio and tubulointerstitial and glomerular fibrosis were less in HFCAT-1 mice than in DCM mice (P<0.05). Renal CAT-1 expression and plasma nitrate and nitrite levels were less in DCM mice compared with WT (P≤0.03) but was greater in HFCAT-1 mice than in DCM mice (P≤0.009). Renal expression of IL-10 was less in DCM mice compared with WT (P<0.001) but was greater in HFCAT-1 mice compared with DCM mice (P=0.02). Our data provide direct evidence that augmented L-arginine transport prevents renal fibrosis, inflammation and loss of kidney function in HF.

ACS Style

Beverly Giam; Haru Nomura; Sanjaya Kuruppu; Po-Yin Chu; Sumia Essid; Helen Kiriazis; Xiao-Jun Du; David M. Kaye; Niwanthi W. Rajapakse. Endothelial-specific overexpression of cationic amino acid transporter-1 prevents loss of kidney function in heart failure. Clinical Science 2020, 134, 2755 -2769.

AMA Style

Beverly Giam, Haru Nomura, Sanjaya Kuruppu, Po-Yin Chu, Sumia Essid, Helen Kiriazis, Xiao-Jun Du, David M. Kaye, Niwanthi W. Rajapakse. Endothelial-specific overexpression of cationic amino acid transporter-1 prevents loss of kidney function in heart failure. Clinical Science. 2020; 134 (20):2755-2769.

Chicago/Turabian Style

Beverly Giam; Haru Nomura; Sanjaya Kuruppu; Po-Yin Chu; Sumia Essid; Helen Kiriazis; Xiao-Jun Du; David M. Kaye; Niwanthi W. Rajapakse. 2020. "Endothelial-specific overexpression of cationic amino acid transporter-1 prevents loss of kidney function in heart failure." Clinical Science 134, no. 20: 2755-2769.

Review article
Published: 18 October 2019 in Clinical Science
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The precise mechanisms underlying resistant hypertension remain elusive. Reduced nitric oxide (NO) bioavailability is frequently documented in chronic kidney disease, obesity, diabetes and advanced age, all of which are risk factors for resistant hypertension. Sympathetic overactivity and chronic activation of the renin–angiotensin system are salient features of resistant hypertension. Interestingly, recent data indicate that renal sympathetic overactivity can reduce the expression of neuronal nitric oxide synthase in the paraventricular nucleus. Reduced NO levels in the paraventricular nucleus can increase sympathetic outflow and this can create a vicious cycle contributing to resistant hypertension. Angiotensin II can reduce l-arginine transport and hence NO production. Reduced NO levels may reduce the formation of angiotensin 1-7 dampening the cardio-protective effects of the renin–angiotensin system contributing to resistant hypertension. In addition, interleukin-6 (IL-6) is demonstrated to be independently associated with resistant hypertension, and IL-6 can reduce NO synthesis. Despite this, NO levels have not been quantified in resistant hypertension. Findings from a small proof of concept study indicate that NO donors can reduce blood pressure in patients with resistant hypertension but more studies are required to validate these preliminary findings. In the present paper, we put forward the hypothesis that reduced NO bioavailability contributes substantially to the development of resistant hypertension.

ACS Style

Niwanthi W. Rajapakse; Beverly Giam; Sanjaya Kuruppu; Geoffrey Head; David M. Kaye. Impaired l-arginine-nitric oxide pathway contributes to the pathogenesis of resistant hypertension. Clinical Science 2019, 133, 2061 -2067.

AMA Style

Niwanthi W. Rajapakse, Beverly Giam, Sanjaya Kuruppu, Geoffrey Head, David M. Kaye. Impaired l-arginine-nitric oxide pathway contributes to the pathogenesis of resistant hypertension. Clinical Science. 2019; 133 (20):2061-2067.

Chicago/Turabian Style

Niwanthi W. Rajapakse; Beverly Giam; Sanjaya Kuruppu; Geoffrey Head; David M. Kaye. 2019. "Impaired l-arginine-nitric oxide pathway contributes to the pathogenesis of resistant hypertension." Clinical Science 133, no. 20: 2061-2067.

Journal article
Published: 16 October 2019 in Toxins
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The binding of compounds to nicotinic acetylcholine receptors is of great interest in biomedical research. However, progress in this area is hampered by the lack of a high-throughput, cost-effective, and taxonomically flexible platform. Current methods are low-throughput, consume large quantities of sample, or are taxonomically limited in which targets can be tested. We describe a novel assay which utilizes a label-free bio-layer interferometry technology, in combination with adapted mimotope peptides, in order to measure ligand binding to the orthosteric site of nicotinic acetylcholine receptor alpha-subunits of diverse organisms. We validated the method by testing the evolutionary patterns of a generalist feeding species (Acanthophis antarcticus), a fish specialist species (Aipysurus laevis), and a snake specialist species (Ophiophagus hannah) for comparative binding to the orthosteric site of fish, amphibian, lizard, snake, bird, marsupial, and rodent alpha-1 nicotinic acetylcholine receptors. Binding patterns corresponded with diet, with the Acanthophis antarcticus not showing bias towards any particular lineage, while Aipysurus laevis showed selectivity for fish, and Ophiophagus hannah a selectivity for snake. To validate the biodiscovery potential of this method, we screened Acanthophis antarcticus and Tropidolaemus wagleri venom for binding to human alpha-1, alpha-2, alpha-3, alpha-4, alpha-5, alpha-6, alpha-7, alpha-9, and alpha-10. While A. antarcticus was broadly potent, T. wagleri showed very strong but selective binding, specifically to the alpha-1 target which would be evolutionarily selected for, as well as the alpha-5 target which is of major interest for drug design and development. Thus, we have shown that our novel method is broadly applicable for studies including evolutionary patterns of venom diversification, predicting potential neurotoxic effects in human envenomed patients, and searches for novel ligands of interest for laboratory tools and in drug design and development.

ACS Style

Christina N. Zdenek; Richard J. Harris; Sanjaya Kuruppu; Nicholas Youngman; James S. Dobson; Jordan Debono; Muzaffar Khan; Ian Smith; Mike Yarski; David Harrich; Charlotte Sweeney; Nathan Dunstan; Luke Allen; Bryan G. Fry. A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors. Toxins 2019, 11, 600 .

AMA Style

Christina N. Zdenek, Richard J. Harris, Sanjaya Kuruppu, Nicholas Youngman, James S. Dobson, Jordan Debono, Muzaffar Khan, Ian Smith, Mike Yarski, David Harrich, Charlotte Sweeney, Nathan Dunstan, Luke Allen, Bryan G. Fry. A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors. Toxins. 2019; 11 (10):600.

Chicago/Turabian Style

Christina N. Zdenek; Richard J. Harris; Sanjaya Kuruppu; Nicholas Youngman; James S. Dobson; Jordan Debono; Muzaffar Khan; Ian Smith; Mike Yarski; David Harrich; Charlotte Sweeney; Nathan Dunstan; Luke Allen; Bryan G. Fry. 2019. "A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors." Toxins 11, no. 10: 600.

Journal article
Published: 01 April 2019 in Toxins
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Russell’s viper (Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication of Russell’s viper envenoming. The mechanism(s) responsible for this effect are unclear. In this study, we examined the cardiovascular effects of Sri Lankan D. russelii venom in anaesthetised rats and in isolated mesenteric arteries. D. russelii venom (100 μg/kg, i.v.) caused a 45 ± 8% decrease in blood pressure within 10 min of administration in anaesthetised (100 μg/kg ketamine/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng/mL–1 μg/mL) caused concentration-dependent relaxation (EC50 = 145.4 ± 63.6 ng/mL, Rmax = 92 ± 2%) in U46619 pre-contracted rat small mesenteric arteries mounted in a myograph. Vasorelaxant potency of venom was unchanged in the presence of the nitric oxide synthase inhibitor, L-NAME (100 µM), or removal of the endothelium. In the presence of high K+ (30 mM), the vasorelaxant response to venom was abolished. Similarly, blocking voltage-dependent (Kv: 4-aminopryidine; 1000 µM) and Ca2+-activated (KCa: tetraethylammonium (TEA; 1000 µM); SKCa: apamin (0.1 µM); IKCa: TRAM-34 (1 µM); BKCa; iberiotoxin (0.1 µM)) K+ channels markedly attenuated venom-induced relaxation. Responses were unchanged in the presence of the ATP-sensitive K+ channel blocker glibenclamide (10 µM), or H1 receptor antagonist, mepyramine (0.1 µM). Venom-induced vasorelaxtion was also markedly decreased in the presence of the transient receptor potential cation channel subfamily V member 4 (TRPV4) antagonist, RN-1734 (10 µM). In conclusion, D. russelii-venom-induced hypotension in rodents may be due to activation of Kv and KCa channels, leading to vasorelaxation predominantly via an endothelium-independent mechanism. Further investigation is required to identify the toxin(s) responsible for this effect.

ACS Style

Rahini Kakumanu; Sanjaya Kuruppu; Lachlan D. Rash; Geoffrey K. Isbister; Wayne C. Hodgson; Barbara K. Kemp-Harper. D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels. Toxins 2019, 11, 197 .

AMA Style

Rahini Kakumanu, Sanjaya Kuruppu, Lachlan D. Rash, Geoffrey K. Isbister, Wayne C. Hodgson, Barbara K. Kemp-Harper. D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels. Toxins. 2019; 11 (4):197.

Chicago/Turabian Style

Rahini Kakumanu; Sanjaya Kuruppu; Lachlan D. Rash; Geoffrey K. Isbister; Wayne C. Hodgson; Barbara K. Kemp-Harper. 2019. "D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels." Toxins 11, no. 4: 197.

Review
Published: 26 February 2019 in Neurochemical Research
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The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer’s disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.

ACS Style

Nkumbu L. Sikanyika; Helena C. Parkington; Ian Smith; Sanjaya Kuruppu. Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer’s Disease. Neurochemical Research 2019, 44, 1289 -1296.

AMA Style

Nkumbu L. Sikanyika, Helena C. Parkington, Ian Smith, Sanjaya Kuruppu. Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer’s Disease. Neurochemical Research. 2019; 44 (6):1289-1296.

Chicago/Turabian Style

Nkumbu L. Sikanyika; Helena C. Parkington; Ian Smith; Sanjaya Kuruppu. 2019. "Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer’s Disease." Neurochemical Research 44, no. 6: 1289-1296.

Research paper
Published: 05 November 2018 in Experimental Physiology
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What is the central question of this study? To determine the reno‐protective effects of serelaxin in the setting of chronic heart failure. What are the main findings and its importance? Our data indicate that serelaxin can reduce renal fibrosis and inflammation in experimental heart failure. Currently, there are no effective treatments to rescue renal function in heart failure patients and our data suggest that serelaxin may have the potential to reduce renal fibrosis and inflammation in heart failure. Abstract Serelaxin has been demonstrated to attenuate renal fibrosis and inflammation in cardiorenal disease. In the present study, we tested the hypothesis that serelaxin can prevent the decline in renal function in dilated cardiomyopathy (DCM) by targeting renal fibrosis and inflammation. Male transgenic mice with DCM (n = 16) and their wild type littermates (WT; n = 20) were administered either vehicle or serelaxin (500 μg kg−1/day; subcutaneous minipumps; eight weeks). Cardiac function was assessed via echocardiography before and during the eighth week of serelaxin treatment. Renal function and inflammation as well as cardiac and renal fibrosis were assessed at study end. Serelaxin had minimal effect on cardiac function (P≥0.99). Tubulointerstitial and glomerular fibrosis were ∼3 fold greater in vehicle treated DCM mice compared to vehicle treated WT (P≤0.001). Renal mRNA expression of Tnfα and Il1α were ∼4 and ∼3 folds greater, respectively, in vehicle treated DCM mice compared to vehicle treated WT (P≤0.05). Tubulointerstitial and glomerular fibrosis were 46% and 45% less respectively, in serelaxin treated DCM mice than in vehicle treated DCM mice (P≤0.01). Renal cortical mRNA expression of Tnfα and Il1α were 56% and 58% less respectively, in the former group compared to the latter (P≤0.05). Urinary albumin:creatinine ratio was ∼3 fold greater in vehicle treated DCM mice compared to vehicle treated WT (P = 0.02). Urinary albumin:creatinine ratio was not significantly different between vehicle treated DCM mice and serelaxin treated DCM mice (P = 0.38). These data suggest that serelaxin can attenuate renal fibrosis and inflammation and has the potential to exert reno‐protective effects in DCM. This article is protected by copyright. All rights reserved

ACS Style

Beverly Giam; Po-Yin Chu; Sanjaya Kuruppu; Ian Smith; Duncan Horlock; Aishwarya Murali; Helen Kiriazis; Xiao-Jun Du; David M. Kaye; Niwanthi Rajapakse. Serelaxin attenuates renal inflammation and fibrosis in a mouse model of dilated cardiomyopathy. Experimental Physiology 2018, 103, 1593 -1602.

AMA Style

Beverly Giam, Po-Yin Chu, Sanjaya Kuruppu, Ian Smith, Duncan Horlock, Aishwarya Murali, Helen Kiriazis, Xiao-Jun Du, David M. Kaye, Niwanthi Rajapakse. Serelaxin attenuates renal inflammation and fibrosis in a mouse model of dilated cardiomyopathy. Experimental Physiology. 2018; 103 (12):1593-1602.

Chicago/Turabian Style

Beverly Giam; Po-Yin Chu; Sanjaya Kuruppu; Ian Smith; Duncan Horlock; Aishwarya Murali; Helen Kiriazis; Xiao-Jun Du; David M. Kaye; Niwanthi Rajapakse. 2018. "Serelaxin attenuates renal inflammation and fibrosis in a mouse model of dilated cardiomyopathy." Experimental Physiology 103, no. 12: 1593-1602.

Review
Published: 04 September 2017 in Pharmacology Research & Perspectives
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Endothelin‐1 (ET‐1) and nitric oxide (NO) are two highly potent vasoactive molecules with opposing effects on the vasculature. Endothelin‐converting enzyme (ECE) and nitric oxide synthase (NOS) catalyse the production of ET‐1 and NO, respectively. It is well established that these molecules play a crucial role in the initiation and progression of cardiovascular diseases and have therefore become targets of therapy. Many studies have examined the mechanism(s) by which NO regulates ET‐1 production. Expression and localization of ECE‐1 is a key factor that determines the rate of ET‐1 production. ECE‐1 can either be membrane bound or be released from the cell surface to produce a soluble form. NO has been shown to reduce the expression of both membrane‐bound and soluble ECE‐1. Several studies have examined the mechanism(s) behind NO‐mediated inhibition of ECE expression on the cell membrane. However, the precise mechanism(s) behind NO‐mediated inhibition of soluble ECE production are unknown. We hypothesize that both exogenous and endogenous NO, inhibits the production of soluble ECE‐1 by preventing its release via extracellular vesicles (e.g., exosomes), and/or by inhibiting the activity of A Disintegrin and Metalloprotease‐17 (ADAM17). If this hypothesis is proven correct in future studies, these pathways represent targets for the therapeutic manipulation of soluble ECE‐1 production.

ACS Style

Sanjaya Kuruppu; Niwanthi W. Rajapakse; Helena C. Parkington; Ian Smith. Pharmacological hypothesis: Nitric oxide-induced inhibition of ADAM-17 activity as well as vesicle release can in turn prevent the production of soluble endothelin-converting enzyme. Pharmacology Research & Perspectives 2017, 5, e00335 .

AMA Style

Sanjaya Kuruppu, Niwanthi W. Rajapakse, Helena C. Parkington, Ian Smith. Pharmacological hypothesis: Nitric oxide-induced inhibition of ADAM-17 activity as well as vesicle release can in turn prevent the production of soluble endothelin-converting enzyme. Pharmacology Research & Perspectives. 2017; 5 (5):e00335.

Chicago/Turabian Style

Sanjaya Kuruppu; Niwanthi W. Rajapakse; Helena C. Parkington; Ian Smith. 2017. "Pharmacological hypothesis: Nitric oxide-induced inhibition of ADAM-17 activity as well as vesicle release can in turn prevent the production of soluble endothelin-converting enzyme." Pharmacology Research & Perspectives 5, no. 5: e00335.

Journal article
Published: 15 July 2017 in American journal of translational research
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ACS Style

Sanjaya Kuruppu; Niwanthi Rajapakse; Helena C Parkington; A Ian Smith. The characteristics of astrocyte on Aβ clearance altered in Alzheimer’s disease were reversed by anti-inflammatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate. American journal of translational research 2017, 9, 3514 -3516.

AMA Style

Sanjaya Kuruppu, Niwanthi Rajapakse, Helena C Parkington, A Ian Smith. The characteristics of astrocyte on Aβ clearance altered in Alzheimer’s disease were reversed by anti-inflammatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate. American journal of translational research. 2017; 9 (7):3514-3516.

Chicago/Turabian Style

Sanjaya Kuruppu; Niwanthi Rajapakse; Helena C Parkington; A Ian Smith. 2017. "The characteristics of astrocyte on Aβ clearance altered in Alzheimer’s disease were reversed by anti-inflammatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate." American journal of translational research 9, no. 7: 3514-3516.

Published erratum
Published: 01 May 2017 in Current Biology
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(Current Biology 27, 1184–1191; April 24, 2017)

ACS Style

Nicholas R. Casewell; Jeroen C. Visser; Kate Baumann; James Dobson; Han Han; Sanjaya Kuruppu; Michael Morgan; Anthony Romilio; Vera Weisbecker; Karine Mardon; Syed A. Ali; Jordan Debono; Ivan Koludarov; Ivo Que; Gregory C. Bird; Gavan M. Cooke; Amanda Nouwens; Wayne Hodgson; Simon C. Wagstaff; Karen L. Cheney; Irina Vetter; Louise Van Der Weerd; Michael K. Richardson; Bryan G. Fry. The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes. Current Biology 2017, 27, 1549 -1550.

AMA Style

Nicholas R. Casewell, Jeroen C. Visser, Kate Baumann, James Dobson, Han Han, Sanjaya Kuruppu, Michael Morgan, Anthony Romilio, Vera Weisbecker, Karine Mardon, Syed A. Ali, Jordan Debono, Ivan Koludarov, Ivo Que, Gregory C. Bird, Gavan M. Cooke, Amanda Nouwens, Wayne Hodgson, Simon C. Wagstaff, Karen L. Cheney, Irina Vetter, Louise Van Der Weerd, Michael K. Richardson, Bryan G. Fry. The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes. Current Biology. 2017; 27 (10):1549-1550.

Chicago/Turabian Style

Nicholas R. Casewell; Jeroen C. Visser; Kate Baumann; James Dobson; Han Han; Sanjaya Kuruppu; Michael Morgan; Anthony Romilio; Vera Weisbecker; Karine Mardon; Syed A. Ali; Jordan Debono; Ivan Koludarov; Ivo Que; Gregory C. Bird; Gavan M. Cooke; Amanda Nouwens; Wayne Hodgson; Simon C. Wagstaff; Karen L. Cheney; Irina Vetter; Louise Van Der Weerd; Michael K. Richardson; Bryan G. Fry. 2017. "The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes." Current Biology 27, no. 10: 1549-1550.

Journal article
Published: 30 March 2017 in Current Biology
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SummaryVenom systems have evolved on multiple occasions across the animal kingdom, and they can act as key adaptations to protect animals from predators [1]. Consequently, venomous animals serve as models for a rich source of mimicry types, as non-venomous species benefit from reductions in predation risk by mimicking the coloration, body shape, and/or movement of toxic counterparts [2–5]. The frequent evolution of such deceitful imitations provides notable examples of phenotypic convergence and are often invoked as classic exemplars of evolution by natural selection. Here, we investigate the evolution of fangs, venom, and mimetic relationships in reef fishes from the tribe Nemophini (fangblennies). Comparative morphological analyses reveal that enlarged canine teeth (fangs) originated at the base of the Nemophini radiation and have enabled a micropredatory feeding strategy in non-venomous Plagiotremus spp. Subsequently, the evolution of deep anterior grooves and their coupling to venom secretory tissue provide Meiacanthus spp. with toxic venom that they effectively employ for defense. We find that fangblenny venom contains a number of toxic components that have been independently recruited into other animal venoms, some of which cause toxicity via interactions with opioid receptors, and result in a multifunctional biochemical phenotype that exerts potent hypotensive effects. The evolution of fangblenny venom has seemingly led to phenotypic convergence via the formation of a diverse array of mimetic relationships that provide protective (Batesian mimicry) and predatory (aggressive mimicry) benefits to other fishes [2, 6]. Our results further our understanding of how novel morphological and biochemical adaptations stimulate ecological interactions in the natural world.

ACS Style

Nicholas R. Casewell; Jeroen C. Visser; Kate Baumann; James Dobson; Han Han; Sanjaya Kuruppu; Michael Morgan; Anthony Romilio; Vera Weisbecker; Karine Mardon; Syed A. Ali; Jordan Debono; Ivan Koludarov; Ivo Que; Gregory C. Bird; Gavan Cooke; Amanda Nouwens; Wayne C. Hodgson; Simon Wagstaff; Karen Cheney; Irina Vetter; Louise van der Weerd; Michael K. Richardson; Bryan G. Fry. The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes. Current Biology 2017, 27, 1184 -1191.

AMA Style

Nicholas R. Casewell, Jeroen C. Visser, Kate Baumann, James Dobson, Han Han, Sanjaya Kuruppu, Michael Morgan, Anthony Romilio, Vera Weisbecker, Karine Mardon, Syed A. Ali, Jordan Debono, Ivan Koludarov, Ivo Que, Gregory C. Bird, Gavan Cooke, Amanda Nouwens, Wayne C. Hodgson, Simon Wagstaff, Karen Cheney, Irina Vetter, Louise van der Weerd, Michael K. Richardson, Bryan G. Fry. The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes. Current Biology. 2017; 27 (8):1184-1191.

Chicago/Turabian Style

Nicholas R. Casewell; Jeroen C. Visser; Kate Baumann; James Dobson; Han Han; Sanjaya Kuruppu; Michael Morgan; Anthony Romilio; Vera Weisbecker; Karine Mardon; Syed A. Ali; Jordan Debono; Ivan Koludarov; Ivo Que; Gregory C. Bird; Gavan Cooke; Amanda Nouwens; Wayne C. Hodgson; Simon Wagstaff; Karen Cheney; Irina Vetter; Louise van der Weerd; Michael K. Richardson; Bryan G. Fry. 2017. "The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes." Current Biology 27, no. 8: 1184-1191.

Research article
Published: 07 March 2017 in Circulation
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Background: Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease. Methods: Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess–treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets. Results: We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens . Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1 , a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart. Conclusions: A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.

ACS Style

Francine Z. Marques; Erin Nelson; Po-Yin Chu; Duncan Horlock; April Fiedler; Mark Ziemann; Jian K. Tan; Sanjaya Kuruppu; Niwanthi W. Rajapakse; Assam El-Osta; Charles R. Mackay; David M. Kaye. High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice. Circulation 2017, 135, 964 -977.

AMA Style

Francine Z. Marques, Erin Nelson, Po-Yin Chu, Duncan Horlock, April Fiedler, Mark Ziemann, Jian K. Tan, Sanjaya Kuruppu, Niwanthi W. Rajapakse, Assam El-Osta, Charles R. Mackay, David M. Kaye. High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice. Circulation. 2017; 135 (10):964-977.

Chicago/Turabian Style

Francine Z. Marques; Erin Nelson; Po-Yin Chu; Duncan Horlock; April Fiedler; Mark Ziemann; Jian K. Tan; Sanjaya Kuruppu; Niwanthi W. Rajapakse; Assam El-Osta; Charles R. Mackay; David M. Kaye. 2017. "High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice." Circulation 135, no. 10: 964-977.

Journal article
Published: 16 February 2017 in Toxins
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Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii and Himantura toshi, and the bony fish Platycephalus fucus, Girella tricuspidata, Mugil cephalus, and Dentex tumifrons. All venoms (10–100 µg/kg, i.v.), except G. tricuspidata and P. fuscus, induced a biphasic response on mean arterial pressure (MAP) in the anesthetised rat. P. fucus venom exhibited a hypotensive response, while venom from G. tricuspidata displayed a single depressor response. All venoms induced cardiovascular collapse at 200 µg/kg, i.v. The in vitro neurotoxic effects of venom were examined using the chick biventer cervicis nerve-muscle (CBCNM) preparation. N. kuhlii, H. toshi, and P. fucus venoms caused concentration-dependent inhibition of indirect twitches in the CBCNM preparation. These three venoms also inhibited responses to exogenous acetylcholine (ACh) and carbachol (CCh), but not potassium chloride (KCl), indicating a post-synaptic mode of action. Venom from G. tricuspidata, M. cephalus, and D. tumifrons had no significant effect on indirect twitches or agonist responses in the CBCNM. Our results demonstrate that envenoming by these species of fish may result in moderate cardiovascular and/or neurotoxic effects. Future studies aimed at identifying the molecules responsible for these effects could uncover potentially novel lead compounds for future pharmaceuticals, in addition to generating new knowledge about the evolutionary relationships between venomous animals.

ACS Style

Han Han; Kate Baumann; Nicholas R. Casewell; Syed A. Ali; James Dobson; Ivan Koludarov; Jordan Debono; Scott C. Cutmore; Niwanthi W. Rajapakse; Timothy N. W. Jackson; Rob Jones; Wayne C. Hodgson; Bryan G. Fry; Sanjaya Kuruppu. The Cardiovascular and Neurotoxic Effects of the Venoms of Six Bony and Cartilaginous Fish Species. Toxins 2017, 9, 67 .

AMA Style

Han Han, Kate Baumann, Nicholas R. Casewell, Syed A. Ali, James Dobson, Ivan Koludarov, Jordan Debono, Scott C. Cutmore, Niwanthi W. Rajapakse, Timothy N. W. Jackson, Rob Jones, Wayne C. Hodgson, Bryan G. Fry, Sanjaya Kuruppu. The Cardiovascular and Neurotoxic Effects of the Venoms of Six Bony and Cartilaginous Fish Species. Toxins. 2017; 9 (2):67.

Chicago/Turabian Style

Han Han; Kate Baumann; Nicholas R. Casewell; Syed A. Ali; James Dobson; Ivan Koludarov; Jordan Debono; Scott C. Cutmore; Niwanthi W. Rajapakse; Timothy N. W. Jackson; Rob Jones; Wayne C. Hodgson; Bryan G. Fry; Sanjaya Kuruppu. 2017. "The Cardiovascular and Neurotoxic Effects of the Venoms of Six Bony and Cartilaginous Fish Species." Toxins 9, no. 2: 67.

Journal article
Published: 04 October 2016 in Journal of Alzheimer's Disease
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Alzheimer's disease is a debilitating neurological disease placing significant burden on health care budgets around the world. It is widely believed that accumulation of amyloid-beta (Aβ) in the brain is a key event that initiates neurodegeneration, thus the clearance of Aβ from brain could be a key therapeutic strategy. Aβ exists in an equilibrium in healthy individuals, and recent research would suggest that dysfunction in the clearance pathways is the driving force behind its accumulation. One mechanism of clearance is proteolytic degradation by enzymes, and increasing the expression of these enzymes in animal models of Alzheimer's disease has indeed shown promising results. This approach could be challenging to translate into the clinic given the likely need for genetic manipulation. We hypothesize that stimulating the activity of these enzymes (as opposed to increasing expression) through pharmacological agents will enhance degradation or at least prevent amyloid deposition, and is therefore another potentially novel avenue to manipulate Aβ levels for therapeutic purposes. We discuss the recent research supporting this hypothesis as well as possible drawbacks to this approach.

ACS Style

Sanjaya Kuruppu; Niwanthi W. Rajapakse; Alexander J. Spicer; Helena C. Parkington; A. Ian Smith. Stimulating the Activity of Amyloid-Beta Degrading Enzymes: A Novel Approach for the Therapeutic Manipulation of Amyloid-Beta Levels. Journal of Alzheimer's Disease 2016, 54, 891 -895.

AMA Style

Sanjaya Kuruppu, Niwanthi W. Rajapakse, Alexander J. Spicer, Helena C. Parkington, A. Ian Smith. Stimulating the Activity of Amyloid-Beta Degrading Enzymes: A Novel Approach for the Therapeutic Manipulation of Amyloid-Beta Levels. Journal of Alzheimer's Disease. 2016; 54 (3):891-895.

Chicago/Turabian Style

Sanjaya Kuruppu; Niwanthi W. Rajapakse; Alexander J. Spicer; Helena C. Parkington; A. Ian Smith. 2016. "Stimulating the Activity of Amyloid-Beta Degrading Enzymes: A Novel Approach for the Therapeutic Manipulation of Amyloid-Beta Levels." Journal of Alzheimer's Disease 54, no. 3: 891-895.

Article
Published: 01 September 2016 in Journal of Hypertension
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Although dietary intake of fruit and vegetables is associated with lower incidence of hypertension, the mechanism involved is not clear. Consumption of a diet high in fibre increases gut microbiota populations that generate short chain fatty acids (SCFAs) such as acetate, which has a protective role in experimental models of inflammatory diseases. Here we established the effect of a high fibre diet and acetate on the development of hypertension and renal function in a mineralocorticoid-excess (MRE) model. Mice were fed control chow (5% fibre), high fibre chow (35% fibre) or water supplemented with acetate for 3 weeks, and then submitted to sham (uninephrectomy) or MRE (uninephrectomy + DOCA tablet) surgeries (n = 11–14/group). At the end of 6 weeks, renal structure and function, blood pressure and gene expression were examined. Compared to MRE mice fed a normal diet, high fibre diet significantly reduced systolic (control DOCA vs high fibre DOCA mean ± SEM: 116 ± 19 mmHg vs 91 ± 5 mmHg, P = 0.0009) and diastolic blood pressure (75 ± 5 mmHg vs 58 ± 5 mmHg, P = 0.0004), glomerular filtration rate (724.8 ± 122 μl/min vs 139.8 ± 23 μl/min, P = 0.023) and urine volume (10.02 ± 3 μl/min vs 2.15 ± 0.8 μl/min, P = 0.032), while there was no change in renal fibrosis. Acetate had a similar effect on blood pressure and renal function, whilst also reduced glomerular and tubulointerstitial fibrosis (all P < 0.05). The protective effects of high fibre and acetate were accompanied by a reduction in immune activation (Cd8a, Ctla4, Il6, Mcp1 and Tlr1 mRNA) together with a decrease in the levels of histone deacetylase 3 (Hdac3) (all P < 0.05), an important epigenetic regulator of immune cell function which also targets the mineralocorticoid receptor. Our data supports that dietary high fibre intake could decrease blood pressure and improve renal function during MRE. The mechanism may involve the SCFA acetate, which had an immunomodulatory role through Hdac3.

ACS Style

Francine Marques; Erin Nelson; Po-Yin Chu; Duncan Horlock; April Fiedler; Sanjaya Kuruppu; Niwanthi Rajapakse; Charles Mackay; David Kaye. MPS 13-02 DIETARY FIBRE INTAKE PREVENTS HYPERTENSION AND IMPROVES RENAL FUNCTION IN A MINERALOCORTICOID-EXCESS MODEL. Journal of Hypertension 2016, 34, e408 .

AMA Style

Francine Marques, Erin Nelson, Po-Yin Chu, Duncan Horlock, April Fiedler, Sanjaya Kuruppu, Niwanthi Rajapakse, Charles Mackay, David Kaye. MPS 13-02 DIETARY FIBRE INTAKE PREVENTS HYPERTENSION AND IMPROVES RENAL FUNCTION IN A MINERALOCORTICOID-EXCESS MODEL. Journal of Hypertension. 2016; 34 (Supplement):e408.

Chicago/Turabian Style

Francine Marques; Erin Nelson; Po-Yin Chu; Duncan Horlock; April Fiedler; Sanjaya Kuruppu; Niwanthi Rajapakse; Charles Mackay; David Kaye. 2016. "MPS 13-02 DIETARY FIBRE INTAKE PREVENTS HYPERTENSION AND IMPROVES RENAL FUNCTION IN A MINERALOCORTICOID-EXCESS MODEL." Journal of Hypertension 34, no. Supplement: e408.

Letter
Published: 19 July 2016 in Circulation
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ACS Style

Niwanthi W. Rajapakse; Sanjaya Kuruppu; A. Ian Smith. Letter by Rajapakse et al Regarding Article, “Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition”. Circulation 2016, 134, e9 -e10.

AMA Style

Niwanthi W. Rajapakse, Sanjaya Kuruppu, A. Ian Smith. Letter by Rajapakse et al Regarding Article, “Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition”. Circulation. 2016; 134 (3):e9-e10.

Chicago/Turabian Style

Niwanthi W. Rajapakse; Sanjaya Kuruppu; A. Ian Smith. 2016. "Letter by Rajapakse et al Regarding Article, “Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition”." Circulation 134, no. 3: e9-e10.

Comparative study
Published: 08 July 2016 in Toxins
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Central and South American pitvipers, belonging to the genera Bothrops and Bothriechis, have independently evolved arboreal tendencies. Little is known regarding the composition and activity of their venoms. In order to close this knowledge gap, venom proteomics and toxin activity of species of Bothriechis, and Bothrops (including Bothriopsis) were investigated through established analytical methods. A combination of proteomics and bioactivity techniques was used to demonstrate a similar diversification of venom composition between large and small species within Bothriechis and Bothriopsis. Increasing our understanding of the evolution of complex venom cocktails may facilitate future biodiscoveries.

ACS Style

Jordan Debono; Chip Cochran; Sanjaya Kuruppu; Amanda Nouwens; Niwanthi W. Rajapakse; Minami Kawasaki; Kelly Wood; James Dobson; Kate Baumann; Mahdokht Jouiaei; Timothy N. W. Jackson; Ivan Koludarov; Dolyce Low; Syed A. Ali; A. Ian Smith; Andrew Barnes; Bryan G. Fry. Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms. Toxins 2016, 8, 210 .

AMA Style

Jordan Debono, Chip Cochran, Sanjaya Kuruppu, Amanda Nouwens, Niwanthi W. Rajapakse, Minami Kawasaki, Kelly Wood, James Dobson, Kate Baumann, Mahdokht Jouiaei, Timothy N. W. Jackson, Ivan Koludarov, Dolyce Low, Syed A. Ali, A. Ian Smith, Andrew Barnes, Bryan G. Fry. Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms. Toxins. 2016; 8 (7):210.

Chicago/Turabian Style

Jordan Debono; Chip Cochran; Sanjaya Kuruppu; Amanda Nouwens; Niwanthi W. Rajapakse; Minami Kawasaki; Kelly Wood; James Dobson; Kate Baumann; Mahdokht Jouiaei; Timothy N. W. Jackson; Ivan Koludarov; Dolyce Low; Syed A. Ali; A. Ian Smith; Andrew Barnes; Bryan G. Fry. 2016. "Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms." Toxins 8, no. 7: 210.

Commentary
Published: 14 June 2016 in Nutrients
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Obesity related hypertension is a major risk factor for resistant hypertension. We do not completely understand the mechanism(s) underlying the development of obesity related hypertension which hinders the development of novel treatment strategies for this condition. Data from experimental studies and small clinical trials indicate that transport of l-arginine, the substrate for nitric oxide (NO), and subsequent NO production are reduced in obesity induced hypertension. Reduced NO bioavailability can induce hypertension via multiple mechanisms. Mirmiran et al. recently analyzed data from a large population study and found that the association between dietary l-arginine and serum nitrate and nitrite was weakened in obese hypertensive subjects compared to obese normotensives. These data suggest that l-arginine dependent NO production is impaired in the former group compared to the latter which may represent a novel mechanism contributing to hypertension in the setting of obesity.

ACS Style

Beverly Giam; Sanjaya Kuruppu; Geoffrey A. Head; David M. Kaye; Niwanthi W. Rajapakse. Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects. Nutrients 2016, 8, 364 .

AMA Style

Beverly Giam, Sanjaya Kuruppu, Geoffrey A. Head, David M. Kaye, Niwanthi W. Rajapakse. Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects. Nutrients. 2016; 8 (6):364.

Chicago/Turabian Style

Beverly Giam; Sanjaya Kuruppu; Geoffrey A. Head; David M. Kaye; Niwanthi W. Rajapakse. 2016. "Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects." Nutrients 8, no. 6: 364.

Journal article
Published: 02 March 2016 in Scientific Reports
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Neprilysin (NEP) and endothelin converting enzyme-1 (ECE-1) are two enzymes that degrade amyloid beta in the brain. Currently there are no molecules to stimulate the activity of these enzymes. Here we report, the discovery and characterisation of a peptide referred to as K49-P1-20, from the venom of Bothrops asper which directly enhances the activity of both ECE-1 and NEP. This is evidenced by a 2- and 5-fold increase in the Vmax of ECE-1 and NEP respectively. The K49-P1-20 concentration required to achieve 50% of maximal stimulation (AC50) of ECE-1 and NEP was 1.92 ± 0.07 and 1.33 ± 0.12 μM respectively. Using BLITZ biolayer interferometry we have shown that K49-P1-20 interacts directly with each enzyme. Intrinsic fluorescence of the enzymes change in the presence of K49-P1-20 suggesting a change in conformation. ECE-1 mediated reduction in the level of endogenous soluble amyloid beta 42 in cerebrospinal fluid is significantly higher in the presence of K49-P1-20 (31 ± 4% of initial) compared with enzyme alone (11 ± 5% of initial; N = 8, P = 0.005, unpaired t-test). K49-P1-20 could be an excellent research tool to study mechanism(s) of enzyme stimulation, and a potential novel drug lead in the fight against Alzheimer’s disease.

ACS Style

A. Ian Smith; Niwanthi Rajapakse; Oded Kleifeld; Bruno Lomonte; Nkumbu L. Sikanyika; Alexander J. Spicer; Wayne Hodgson; Paul Conroy; David H. Small; David M. Kaye; Helena C. Parkington; James Whisstock; Sanjaya Kuruppu. N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin. Scientific Reports 2016, 6, 22413 .

AMA Style

A. Ian Smith, Niwanthi Rajapakse, Oded Kleifeld, Bruno Lomonte, Nkumbu L. Sikanyika, Alexander J. Spicer, Wayne Hodgson, Paul Conroy, David H. Small, David M. Kaye, Helena C. Parkington, James Whisstock, Sanjaya Kuruppu. N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin. Scientific Reports. 2016; 6 (1):22413.

Chicago/Turabian Style

A. Ian Smith; Niwanthi Rajapakse; Oded Kleifeld; Bruno Lomonte; Nkumbu L. Sikanyika; Alexander J. Spicer; Wayne Hodgson; Paul Conroy; David H. Small; David M. Kaye; Helena C. Parkington; James Whisstock; Sanjaya Kuruppu. 2016. "N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin." Scientific Reports 6, no. 1: 22413.

Journal article
Published: 01 August 2015 in Toxicon
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Brown snake (Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 µg/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 µg/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 µg/ml), but not fraction 3 (1 or 3 µg/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom

ACS Style

Janeyuth Chaisakul; Geoffrey K. Isbister; Margaret O'Leary; Helena C. Parkington; Ian Smith; Wayne Hodgson; Sanjaya Kuruppu. Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis. Toxicon 2015, 102, 48 -54.

AMA Style

Janeyuth Chaisakul, Geoffrey K. Isbister, Margaret O'Leary, Helena C. Parkington, Ian Smith, Wayne Hodgson, Sanjaya Kuruppu. Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis. Toxicon. 2015; 102 ():48-54.

Chicago/Turabian Style

Janeyuth Chaisakul; Geoffrey K. Isbister; Margaret O'Leary; Helena C. Parkington; Ian Smith; Wayne Hodgson; Sanjaya Kuruppu. 2015. "Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis." Toxicon 102, no. : 48-54.

Journal article
Published: 17 September 2014 in Molecular and Cellular Biochemistry
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This study examined the effect of nitric oxide on the production of soluble ECE-1. Activity of ECE-1 in media was measured using a quenched fluorescent substrate assay, and expressed as a percentage of control. Endothelial cells were incubated with the nitric oxide donor Diethylenetriamine NONOate (DETA; 250–800 µM), NOS substrate l-Arg (200–1,000 µM), a l-Arg transport inhibitor (l-Lys; 10 µM) and NOS inhibitors (l-Gln and N5-[imino(nitroamino)methyl]-l-ornithine, methyl ester, monohydrochloride (l-NAME); 10–100 µM). The effect of l-Arg (1,000 µM) was also tested in the presence of l-Lys (10 µM), l-Gln (100 µM) and l-NAME (10–100 µM). Ultracentrifugation (100,000×g, 4 °C, 1 h) completely removed ECE-1 activity from the supernatant. In addition, fractionation of concentrated media on a sucrose density gradient indicated that ECE-1 activity was localised to the mid portion of the gradient, thus suggesting the possible role of exosomes in ECE-1 release. Production of soluble ECE-1 by Ea.hy926 cells was inhibited significantly (P t test, n = 4) in the presence of DETA (75.31 ± 3.59; 800 µM) and l-Arg (60.97 ± 9.22; 1,000 µM). l-Arg-mediated reduction in the release of soluble ECE-1 was blocked by the inhibition of NOS using l-NAME (100 µM; 99.19 ± 0.58) and l-Gln (100 µM; 104.41 ± 0.65). In addition, the presence of l-Lys (10 µM) significantly blocked the l-Arg (1,000 µM)-induced reduction in soluble ECE-1 levels (122.38 ± 13.16). These treatments had no effect on the expression of ECE-1 on the cell surface. Our data provide evidence that NO can inhibit the production of soluble ECE-1 by endothelial cells.

ACS Style

Sanjaya Kuruppu; Niwanthi W. Rajapakse; Rhys A. Dunstan; Ian Smith. Nitric oxide inhibits the production of soluble endothelin converting enzyme-1. Molecular and Cellular Biochemistry 2014, 396, 49 -54.

AMA Style

Sanjaya Kuruppu, Niwanthi W. Rajapakse, Rhys A. Dunstan, Ian Smith. Nitric oxide inhibits the production of soluble endothelin converting enzyme-1. Molecular and Cellular Biochemistry. 2014; 396 (1):49-54.

Chicago/Turabian Style

Sanjaya Kuruppu; Niwanthi W. Rajapakse; Rhys A. Dunstan; Ian Smith. 2014. "Nitric oxide inhibits the production of soluble endothelin converting enzyme-1." Molecular and Cellular Biochemistry 396, no. 1: 49-54.