This page has only limited features, please log in for full access.

Unclaimed
Kenneth J. Rodgers
Neurotoxin Research Group, School of Life Sciences, University of Technology Syd, ney, Faculty of Science, Sydney, Australia

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Original article
Published: 20 July 2021 in Amino Acids
Reads 0
Downloads 0

The cyanobacterial non-protein amino acid α-amino-β-methylaminopropionic acid, more commonly known as BMAA, was first discovered in the seeds of the ancient gymnosperm Cycad circinalis (now Cycas micronesica Hill). BMAA was linked to the high incidence of neurological disorders on the island of Guam first reported in the 1950s. BMAA still attracts interest as a possible causative factor in amyotrophic lateral sclerosis (ALS) following the identification of ALS disease clusters associated with living in proximity to lakes with regular cyanobacterial blooms. Since its discovery, BMAA toxicity has been the subject of many in vivo and in vitro studies. A number of mechanisms of toxicity have been proposed including an agonist effect at glutamate receptors, competition with cysteine for transport system xc_ and other mechanisms capable of generating cellular oxidative stress. In addition, a wide range of studies have reported effects related to disturbances in proteostasis including endoplasmic reticulum stress and activation of the unfolded protein response. In the present studies we examine the effects of BMAA on the ubiquitin-proteasome system (UPS) and on chaperone-mediated autophagy (CMA) by measuring levels of ubiquitinated proteins and lamp2a protein levels in a differentiated neuronal cell line exposed to BMAA. The BMAA induced increases in oxidised proteins and the increase in CMA activity reported could be prevented by co-administration of L-serine but not by the two antioxidants examined. These data provide further evidence of a protective role for L-serine against the deleterious effects of BMAA.

ACS Style

Adam W. Quinn; Connor R. Phillips; Jake P. Violi; Joel R. Steele; Michael S. Johnson; Mika T. Westerhausen; Kenneth J. Rodgers. β-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine. Amino Acids 2021, 1 -9.

AMA Style

Adam W. Quinn, Connor R. Phillips, Jake P. Violi, Joel R. Steele, Michael S. Johnson, Mika T. Westerhausen, Kenneth J. Rodgers. β-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine. Amino Acids. 2021; ():1-9.

Chicago/Turabian Style

Adam W. Quinn; Connor R. Phillips; Jake P. Violi; Joel R. Steele; Michael S. Johnson; Mika T. Westerhausen; Kenneth J. Rodgers. 2021. "β-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine." Amino Acids , no. : 1-9.

Journal article
Published: 08 July 2021 in Research in Microbiology
Reads 0
Downloads 0

In contrast to mammalian cells, bacteria such as E. coli have been shown to display tolerance towards the neurotoxin β-methylamino-L-alanine (BMAA) suggesting that these prokaryotes possess a way to metabolise BMAA resulting in its export, degradation, or detoxification. Single gene deletion mutants of E. coli K-12 with inactivated amino acid biosynthesis pathways were treated with 500 μg/ml BMAA and the resulting growth was monitored. Wild type E. coli and the majority of gene deletion mutants displayed unaltered growth in the presence of BMAA over 12 hours. Conversely, deletion of the gene cysE, a key component of the cysteine biosynthesis pathway, was shown to result in susceptibility to BMAA and a lack of growth in a dose-dependent manner. This strain also showed increased susceptibility to oxidative stress in the form of H2O2, and disruptions in glutathione levels. The cysteine biosynthesis pathway is linked to the tolerance of BMAA in E. coli, and potentially represents a mechanism of BMAA detoxification.

ACS Style

Carly J. Italiano; Lisa Pu; Jake P. Violi; Iain G. Duggin; Kenneth J. Rodgers. Cysteine biosynthesis contributes to β-methylamino-l-alanine tolerance in Escherichia coli. Research in Microbiology 2021, 103852 .

AMA Style

Carly J. Italiano, Lisa Pu, Jake P. Violi, Iain G. Duggin, Kenneth J. Rodgers. Cysteine biosynthesis contributes to β-methylamino-l-alanine tolerance in Escherichia coli. Research in Microbiology. 2021; ():103852.

Chicago/Turabian Style

Carly J. Italiano; Lisa Pu; Jake P. Violi; Iain G. Duggin; Kenneth J. Rodgers. 2021. "Cysteine biosynthesis contributes to β-methylamino-l-alanine tolerance in Escherichia coli." Research in Microbiology , no. : 103852.

Journal article
Published: 24 May 2021 in Proteomes
Reads 0
Downloads 0

Proteinopathies are protein misfolding diseases that have an underlying factor that affects the conformation of proteoforms. A factor hypothesised to play a role in these diseases is the incorporation of non-protein amino acids into proteins, with a key example being the therapeutic drug levodopa. The presence of levodopa as a protein constituent has been explored in several studies, but it has not been examined in a global proteomic manner. This paper provides a proof-of-concept method for enzymatically creating levodopa-containing proteins using the enzyme tyrosinase and provides spectral evidence of in vitro incorporation in addition to the induction of the unfolded protein response due to levodopa.

ACS Style

Joel Steele; Natalie Strange; Kenneth Rodgers; Matthew Padula. A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation. Proteomes 2021, 9, 24 .

AMA Style

Joel Steele, Natalie Strange, Kenneth Rodgers, Matthew Padula. A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation. Proteomes. 2021; 9 (2):24.

Chicago/Turabian Style

Joel Steele; Natalie Strange; Kenneth Rodgers; Matthew Padula. 2021. "A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation." Proteomes 9, no. 2: 24.

Review
Published: 21 January 2021 in Proteomes
Reads 0
Downloads 0

Proteinopathies are diseases caused by factors that affect proteoform conformation. As such, a prevalent hypothesis is that the misincorporation of noncanonical amino acids into a proteoform results in detrimental structures. However, this hypothesis is missing proteomic evidence, specifically the detection of a noncanonical amino acid in a peptide sequence. This review aims to outline the current state of technology that can be used to investigate mistranslations and misincorporations whilst framing the pursuit as Misincorporation Proteomics (MiP). The current availability of technologies explored herein is mass spectrometry, sample enrichment/preparation, data analysis techniques, and the hyphenation of approaches. While many of these technologies show potential, our review reveals a need for further development and refinement of approaches is still required.

ACS Style

Joel Steele; Carly Italiano; Connor Phillips; Jake Violi; Lisa Pu; Kenneth Rodgers; Matthew Padula. Misincorporation Proteomics Technologies: A Review. Proteomes 2021, 9, 2 .

AMA Style

Joel Steele, Carly Italiano, Connor Phillips, Jake Violi, Lisa Pu, Kenneth Rodgers, Matthew Padula. Misincorporation Proteomics Technologies: A Review. Proteomes. 2021; 9 (1):2.

Chicago/Turabian Style

Joel Steele; Carly Italiano; Connor Phillips; Jake Violi; Lisa Pu; Kenneth Rodgers; Matthew Padula. 2021. "Misincorporation Proteomics Technologies: A Review." Proteomes 9, no. 1: 2.

Review article
Published: 24 August 2020 in TrAC Trends in Analytical Chemistry
Reads 0
Downloads 0

Amino acids are present in a variety of matrices from biological fluids to plant and animal tissues. We discuss options for amino acid extraction, sample clean up and protein hydrolysis. Chromatographic separation of native amino acids is difficult due to their structure and physiochemical properties. Most analysts derivatise amino acids prior to analysis which improves the signal to noise ratio, provides more efficient ionisation and allows the use of reverse phase chromatography. Since chiral analysis is becoming increasingly important, we discuss chiral column chromatography and the use of chiral derivatisation agents. The choice of detector and parameters is based on a wide array of criteria including whether amino acids are native or derivatised and if targeted or untargeted analysis is being performed. This tutorial review aims to act as both a guide and to provide an overview of the techniques scientists currently employ for the analysis of amino acids via liquid chromatography-tandem mass spectrometry.

ACS Style

Jake P. Violi; David P. Bishop; Matthew P. Padula; Joel R. Steele; Kenneth J. Rodgers. Considerations for amino acid analysis by liquid chromatography-tandem mass spectrometry: A tutorial review. TrAC Trends in Analytical Chemistry 2020, 131, 116018 .

AMA Style

Jake P. Violi, David P. Bishop, Matthew P. Padula, Joel R. Steele, Kenneth J. Rodgers. Considerations for amino acid analysis by liquid chromatography-tandem mass spectrometry: A tutorial review. TrAC Trends in Analytical Chemistry. 2020; 131 ():116018.

Chicago/Turabian Style

Jake P. Violi; David P. Bishop; Matthew P. Padula; Joel R. Steele; Kenneth J. Rodgers. 2020. "Considerations for amino acid analysis by liquid chromatography-tandem mass spectrometry: A tutorial review." TrAC Trends in Analytical Chemistry 131, no. : 116018.

Journal article
Published: 22 October 2019 in The International Journal of Biochemistry & Cell Biology
Reads 0
Downloads 0

In Parkinson's disease (PD), as in many other neurodegenerative disorders, mitochondrial dysfunction, protein misfolding, and proteotoxic stress underly the disease process. For decades, the primary symptomatic treatment for PD has been the dopamine precursor L-DOPA (Levodopa). L-DOPA however can initiate protein misfolding through its ability to mimic the protein amino acid L-tyrosine, resulting in random errors in aminoacylation and L-DOPA becoming mistakenly inserted into the polypeptide chain of proteins in place of L-tyrosine. In the present study we examined the impact that the generation of DOPA-containing proteins had on human neuroblastoma cell (SH-SY5Y) function in vitro. We showed that even in the presence of antioxidants there was a significant accumulation of cytosolic ubiquitin in DOPA-treated cells, an upregulation in the endosomal-lysosomal degradation system, deleterious changes to mitochondrial morphology and a marked decline in mitochondrial function.The effects of L-DOPA on mitochondrial function were not observed with D-DOPA, the stereoisomer of L-DOPA that cannot be inserted into proteins so did not result from oxidative stress. We could fully protect against these effects by co-treatment with L-tyrosine, supporting the view that misincorporation of L-DOPA into proteins contributed to these cytotoxic effects, leading us to suggest that co-treatment with L-tyrosine could be beneficial therapeutically.

ACS Style

Steven Giannopoulos; Kate Samardzic; Benjamin B.A. Raymond; Steven Djordjevic; Kenneth J. Rodgers. L-DOPA causes mitochondrial dysfunction in vitro: A novel mechanism of L-DOPA toxicity uncovered. The International Journal of Biochemistry & Cell Biology 2019, 117, 105624 .

AMA Style

Steven Giannopoulos, Kate Samardzic, Benjamin B.A. Raymond, Steven Djordjevic, Kenneth J. Rodgers. L-DOPA causes mitochondrial dysfunction in vitro: A novel mechanism of L-DOPA toxicity uncovered. The International Journal of Biochemistry & Cell Biology. 2019; 117 ():105624.

Chicago/Turabian Style

Steven Giannopoulos; Kate Samardzic; Benjamin B.A. Raymond; Steven Djordjevic; Kenneth J. Rodgers. 2019. "L-DOPA causes mitochondrial dysfunction in vitro: A novel mechanism of L-DOPA toxicity uncovered." The International Journal of Biochemistry & Cell Biology 117, no. : 105624.

Journal article
Published: 02 September 2019 in Toxins
Reads 0
Downloads 0

β-methylamino-L-alanine (BMAA) is a non-protein amino acid that has been implicated as a risk factor for motor neurone disease (MND). BMAA is produced by a wide range of cyanobacteria globally and by a small number of marine diatoms. BMAA is commonly found with two of its constitutional isomers: 2,4-diaminobutyric acid (2,4-DAB), and N-(2-aminoethyl)glycine (AEG). The isomer 2,4-DAB, like BMAA, has neurotoxic properties. While many studies have shown BMAA production by cyanobacteria, few studies have looked at other algal groups. Several studies have shown BMAA production by marine diatoms; however, there are no studies examining freshwater diatoms. This study aimed to determine if some freshwater diatoms produced BMAA, and which diatom taxa are capable of BMAA, 2,4-DAB and AEG production. Five axenic diatom cultures were established from river and lake sites across eastern Australia. Cultures were harvested during the stationary growth phase and intracellular amino acids were extracted. Using liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS), diatom extracts were analysed for the presence of both free and protein-associated BMAA, 2,4-DAB and AEG. Of the five diatom cultures analysed, four were found to have detectable BMAA and AEG, while 2,4-DAB was found in all cultures. These results show that BMAA production by diatoms is not confined to marine genera and that the prevalence of these non-protein amino acids in Australian freshwater environments cannot be solely attributed to cyanobacteria.

ACS Style

Jake P. Violi; Jordan A. Facey; Simon M. Mitrovic; Anne Colville; Kenneth J. Rodgers. Production of β-methylamino-L-alanine (BMAA) and Its Isomers by Freshwater Diatoms. Toxins 2019, 11, 512 .

AMA Style

Jake P. Violi, Jordan A. Facey, Simon M. Mitrovic, Anne Colville, Kenneth J. Rodgers. Production of β-methylamino-L-alanine (BMAA) and Its Isomers by Freshwater Diatoms. Toxins. 2019; 11 (9):512.

Chicago/Turabian Style

Jake P. Violi; Jordan A. Facey; Simon M. Mitrovic; Anne Colville; Kenneth J. Rodgers. 2019. "Production of β-methylamino-L-alanine (BMAA) and Its Isomers by Freshwater Diatoms." Toxins 11, no. 9: 512.

Original article
Published: 13 July 2019 in Amino Acids
Reads 0
Downloads 0

In addition to the 20 protein amino acids that are vital to human health, hundreds of naturally occurring amino acids, known as non-proteinogenic amino acids (NPAAs), exist and can enter the human food chain. Some NPAAs are toxic through their ability to mimic protein amino acids and this property is utilised by NPAA-containing plants to inhibit the growth of other plants or kill herbivores. The NPAA l-azetidine-2-carboxylic acid (Aze) enters the food chain through the use of sugar beet (Beta vulgaris) by-products as feed in the livestock industry and may also be found in sugar beet by-product fibre supplements. Aze mimics the protein amino acid l-proline and readily misincorporates into proteins. In light of this, we examined the toxicity of Aze to mammalian cells in vitro. We showed decreased viability in Aze-exposed cells with both apoptotic and necrotic cell death. This was accompanied by alterations in endosomal–lysosomal activity, changes to mitochondrial morphology and a significant decline in mitochondrial function. In summary, the results show that Aze exposure can lead to deleterious effects on human neuron-like cells and highlight the importance of monitoring human Aze consumption via the food chain.

ACS Style

Kate Samardzic; Kenneth J. Rodgers. Cell death and mitochondrial dysfunction induced by the dietary non-proteinogenic amino acid l-azetidine-2-carboxylic acid (Aze). Amino Acids 2019, 51, 1221 -1232.

AMA Style

Kate Samardzic, Kenneth J. Rodgers. Cell death and mitochondrial dysfunction induced by the dietary non-proteinogenic amino acid l-azetidine-2-carboxylic acid (Aze). Amino Acids. 2019; 51 (8):1221-1232.

Chicago/Turabian Style

Kate Samardzic; Kenneth J. Rodgers. 2019. "Cell death and mitochondrial dysfunction induced by the dietary non-proteinogenic amino acid l-azetidine-2-carboxylic acid (Aze)." Amino Acids 51, no. 8: 1221-1232.

Journal article
Published: 01 May 2019 in Ecotoxicology and Environmental Safety
Reads 0
Downloads 0

Environmental exposure to the amino acid β-methylamino-L-alanine (BMAA) was linked to the high incidence of neurodegenerative disease first reported on the island of Guam in the 1940s and has more recently been implicated in an increased incidence of amyotrophic lateral sclerosis (ALS) in parts of the USA. BMAA has been shown to be produced by a range of cyanobacteria and some marine diatoms and dinoflagellates in different parts of the world. BMAA is commonly found with two of its constitutional isomers: 2,4- diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl) glycine (AEG). These isomers are thought to be co-produced by the same organisms that produce BMAA and MS/MS analysis following LC separation can add an additional level of specificity over LC-FL. Although the presence of BMAA and 2,4-DAB in surface scum samples from several sites in Australia has been reported, which Australian cyanobacterial species are capable of BMAA, 2,4-DAB and AEG production remains unknown. The aims of the present studies were to identify some of the cyanobacterial genera or species that can produce BMAA, 2,4-DAB and AEG in freshwater cyanobacteria blooms in eastern Australia. Eleven freshwater sites were sampled and from these, 19 single-species cyanobacterial cultures were established. Amino acids were extracted from cyanobacterial cultures and analysed using liquid chromatography-tandem mass spectrometry. BMAA was detected in 17 of the 19 isolates, 2,4-DAB was detected in all isolates, and AEG was detected in 18 of the 19 isolates, showing the prevalence of these amino acids in Australian freshwater cyanobacteria. Concentrations of all three isomers in Australian cyanobacteria were generally higher than the concentrations reported elsewhere. This study confirmed the presence of BMAA and its isomers in cyanobacteria isolated from eastern Australian freshwater systems, and determined which Australian cyanobacterial genera or species were capable of producing them when cultured under laboratory conditions.

ACS Style

Jake P. Violi; Simon Mitrovic; Anne Colville; Brendan J. Main; Kenneth J. Rodgers. Prevalence of β-methylamino-L-alanine (BMAA) and its isomers in freshwater cyanobacteria isolated from eastern Australia. Ecotoxicology and Environmental Safety 2019, 172, 72 -81.

AMA Style

Jake P. Violi, Simon Mitrovic, Anne Colville, Brendan J. Main, Kenneth J. Rodgers. Prevalence of β-methylamino-L-alanine (BMAA) and its isomers in freshwater cyanobacteria isolated from eastern Australia. Ecotoxicology and Environmental Safety. 2019; 172 ():72-81.

Chicago/Turabian Style

Jake P. Violi; Simon Mitrovic; Anne Colville; Brendan J. Main; Kenneth J. Rodgers. 2019. "Prevalence of β-methylamino-L-alanine (BMAA) and its isomers in freshwater cyanobacteria isolated from eastern Australia." Ecotoxicology and Environmental Safety 172, no. : 72-81.

Journal article
Published: 29 January 2019 in Toxicology in Vitro
Reads 0
Downloads 0

In addition to the 20 protein amino acids that are encoded for protein synthesis, hundreds of other naturally occurring amino acids, known as non-proteinogenic amino acids (NPAAs) exist. It is well known that some NPAAs are toxic through their ability to mimic protein amino acids, either in protein synthesis or in other metabolic pathways, and this property is utilised by some plants to inhibit the growth of other plants or kill herbivores. L-norvaline is an NPAA readily available for purchase as a dietary supplement. In light of previous evidence of l-norvaline's antifungal, antimicrobial and herbicidal activity, we examined the toxicity of l-norvaline to mammalian cells in vitro and showed that l-norvaline decreased cell viability at concentrations as low as 125 μM, caused necrotic cell death and significant changes to mitochondrial morphology and function. Furthermore, toxicity was reduced in the presence of structurally similar ‘protein’ amino acids, suggesting l-norvaline's cytotoxicity could be attributed to protein amino acid mimicry.

ACS Style

Kate Samardzic; Kenneth J. Rodgers. Cytotoxicity and mitochondrial dysfunction caused by the dietary supplement l-norvaline. Toxicology in Vitro 2019, 56, 163 -171.

AMA Style

Kate Samardzic, Kenneth J. Rodgers. Cytotoxicity and mitochondrial dysfunction caused by the dietary supplement l-norvaline. Toxicology in Vitro. 2019; 56 ():163-171.

Chicago/Turabian Style

Kate Samardzic; Kenneth J. Rodgers. 2019. "Cytotoxicity and mitochondrial dysfunction caused by the dietary supplement l-norvaline." Toxicology in Vitro 56, no. : 163-171.

Journal article
Published: 27 March 2018 in Harmful Algae
Reads 0
Downloads 0

The emerging toxin β-methylamino-l-alanine (BMAA) has been linked to the development of a number of neurodegenerative diseases in humans including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease. BMAA has been found to be produced by a range of cyanobacteria, diatoms, and dinoflagellates worldwide, and is present in freshwater, saltwater, and terrestrial ecosystems. Surface scum samples were collected from waterways in rural and urban New South Wales, Australia and algal species identified. Reverse phase liquid chromatography-tandem mass spectrometry was used to analyse sixteen cyanobacterial scum for the presence of BMAA as well as its toxic structural isomer 2,4-diaminobutyric acid (2,4-DAB). BMAA was detected in ten of the samples analysed, and 2,4-DAB in all sixteen. The presence of these toxins in water used for agriculture raises concerns for public health and food security in Australia.

ACS Style

Brendan J. Main; Lee Bowling; Matthew Padula; David Bishop; Simon Mitrovic; Gilles Guillemin; Kenneth J. Rodgers. Detection of the suspected neurotoxin β-methylamino- l -alanine (BMAA) in cyanobacterial blooms from multiple water bodies in Eastern Australia. Harmful Algae 2018, 74, 10 -18.

AMA Style

Brendan J. Main, Lee Bowling, Matthew Padula, David Bishop, Simon Mitrovic, Gilles Guillemin, Kenneth J. Rodgers. Detection of the suspected neurotoxin β-methylamino- l -alanine (BMAA) in cyanobacterial blooms from multiple water bodies in Eastern Australia. Harmful Algae. 2018; 74 ():10-18.

Chicago/Turabian Style

Brendan J. Main; Lee Bowling; Matthew Padula; David Bishop; Simon Mitrovic; Gilles Guillemin; Kenneth J. Rodgers. 2018. "Detection of the suspected neurotoxin β-methylamino- l -alanine (BMAA) in cyanobacterial blooms from multiple water bodies in Eastern Australia." Harmful Algae 74, no. : 10-18.

Original article
Published: 12 December 2017 in Amino Acids
Reads 0
Downloads 0

There is a strong body of evidence linking the non-protein amino acid (NPAA) β-methylamino-l-alanine (BMAA) to the development of a number of neurodegenerative diseases. BMAA has been found globally, is produced by a number of organisms including cyanobacteria, diatoms, and dinoflagellates; and has been shown to biomagnify through trophic levels. The role of BMAA in neurodegenerative disease is highlighted by its presence in the brains of a number of neurodegenerative disease patients, where it was found in a protein-bound form. We have previously shown that BMAA is bound to cell proteins, and results in the upregulation of the unfolded protein response, an endoplasmic reticulum stress response activated by the presence of misfolded proteins within the cell. Structurally aberrant proteins are features of a number of neurodegenerative diseases, and further investigation of how BMAA interacts with proteins is crucial to our understanding of its toxicity. Here we use radiolabelled BMAA to investigate the interaction and binding of BMAA to eukaryotic and prokaryotic proteins. We found differences in the presence and distribution of protein-bound BMAA between E. coli and neuroblastoma cells, with an increase in binding over time only seen in the eukaryotic cells. We also found that BMAA was unable to bind to pure proteins, or cell lysate in native or denaturing conditions, indicating that biological processing is required for BMAA to bind to proteins.

ACS Style

Brendan Main; Carly Italiano; Kenneth J. Rodgers. Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins. Amino Acids 2017, 50, 397 -407.

AMA Style

Brendan Main, Carly Italiano, Kenneth J. Rodgers. Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins. Amino Acids. 2017; 50 (3-4):397-407.

Chicago/Turabian Style

Brendan Main; Carly Italiano; Kenneth J. Rodgers. 2017. "Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins." Amino Acids 50, no. 3-4: 397-407.

Original article
Published: 20 June 2017 in Neurotoxicity Research
Reads 0
Downloads 0

The non-protein amino acid (NPAA) ß-methylamino-l-alanine (BMAA) is produced by a diverse range of cyanobacteria, diatoms and dinoflagellates, and is present in both aquatic and terrestrial ecosystems globally. Exposure to BMAA has been implicated in the development of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). BMAA is often found in nature along with its structural isomers 2,4-diaminobutyric acid (2,4-DAB) and aminoethylglycine (AEG); however, the toxicity of these NPAAs in combination has not been examined. We have previously demonstrated that BMAA induces endoplasmic reticulum (ER) stress and increases caspase and cathepsin activity in human neuroblastoma cells (SH-SY5Y), effects consistent with proteotoxic stress due to disturbances in protein synthesis, folding or turnover. The current study investigates whether 2,4-DAB and AEG share a similar mechanism of toxicity to BMAA, and if simultaneous exposure of cells to BMAA and its isomers results in increased toxicity in vitro. We show that a 48-h treatment with both 500 μM BMAA and 2,4-DAB decreases cell viability in vitro whereas AEG was not cytotoxic under the same conditions. Treatment of SH-SY5Y cells with 2,4-DAB did not increase expression of ER stress markers. Combined treatment of cells with BMAA and 2,4-DAB resulted in increased caspase activity and increased apoptosis above that of BMAA or 2,4-DAB on their own. These results suggest that 2,4-DAB does not share the same mechanism of toxicity as BMAA but the presence of 2,4-DAB increases the toxicity of BMAA to human cells in vitro.

ACS Style

Brendan Main; Kenneth J. Rodgers. Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells. Neurotoxicity Research 2017, 33, 33 -42.

AMA Style

Brendan Main, Kenneth J. Rodgers. Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells. Neurotoxicity Research. 2017; 33 (1):33-42.

Chicago/Turabian Style

Brendan Main; Kenneth J. Rodgers. 2017. "Assessing the Combined Toxicity of BMAA and Its Isomers 2,4-DAB and AEG In Vitro Using Human Neuroblastoma Cells." Neurotoxicity Research 33, no. 1: 33-42.

Review
Published: 09 June 2017 in Biological Chemistry
Reads 0
Downloads 0

The ‘oxygen paradox’ arises from the fact that oxygen, the molecule that aerobic life depends on, threatens its very existence. An oxygen-rich environment provided life on Earth with more efficient bioenergetics and, with it, the challenge of having to deal with a host of oxygen-derived reactive species capable of damaging proteins and other crucial cellular components. In this minireview, we explore recent insights into the metabolism of proteins that have been reversibly or irreversibly damaged by oxygen-derived species. We discuss recent data on the important roles played by the proteasomal and lysosomal systems in the proteolytic degradation of oxidatively damaged proteins and the effects of oxidative damage on the function of the proteolytic pathways themselves. Mitochondria are central to oxygen utilisation in the cell, and their ability to handle oxygen-derived radicals is an important and still emerging area of research. Current knowledge of the proteolytic machinery in the mitochondria, including the ATP-dependent AAA+ proteases and mitochondrial-derived vesicles, is also highlighted in the review. Significant progress is still being made in regard to understanding the mechanisms underlying the detection and degradation of oxidised proteins and how proteolytic pathways interact with each other. Finally, we highlight a few unanswered questions such as the possibility of oxidised amino acids released from oxidised proteins by proteolysis being re-utilised in protein synthesis thus establishing a vicious cycle of oxidation in cells.

ACS Style

Kate Samardzic; Kenneth J. Rodgers. Oxidised protein metabolism: recent insights. Biological Chemistry 2017, 398, 1165 -1175.

AMA Style

Kate Samardzic, Kenneth J. Rodgers. Oxidised protein metabolism: recent insights. Biological Chemistry. 2017; 398 (11):1165-1175.

Chicago/Turabian Style

Kate Samardzic; Kenneth J. Rodgers. 2017. "Oxidised protein metabolism: recent insights." Biological Chemistry 398, no. 11: 1165-1175.

Review
Published: 05 June 2017 in Neurotoxicity Research
Reads 0
Downloads 0

Cyanobacteria are some of the oldest organisms on earth, and have evolved to produce a battery of toxic metabolites, including hepatotoxins, dermatoxins, and neurotoxins. In this review, we focus on the occurrence and mechanisms of toxicity of a number of neurotoxins synthesised by these ancient photosynthetic prokaryotes. We discuss the evidence linking β-methylamino-L-alanine (BMAA), a non-protein amino acid, to an unusual neurological disease complex reported on the island of Guam in the 1950s, and how 60 years later, the role that BMAA plays in human disease is still unclear. There is now evidence that BMAA is also produced by some eukaryotes, and can bioaccumulate in food chains; this combined with higher frequency of cyanobacterial blooms globally, increases the potential for human exposure. Three BMAA isomers that often co-occur with BMAA have been identified, and the current knowledge on the toxicity of these molecules is presented. The acute alkaloid toxins; anatoxin-a, homoanatoxin-a and the saxitoxins, and the organophosphate neurotoxin anatoxin-a(S) are also discussed. In many cases, human exposure to a cocktail of cyanobacterial neurotoxins is likely; however, the implications of combined exposure to these toxins have not been fully explored. Increased understanding of the combined effects of cyanobacterial neurotoxins is required to fully understand how these molecules impact on human health.

ACS Style

Kenneth J. Rodgers; Brendan Main; Kate Samardzic. Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity. Neurotoxicity Research 2017, 33, 168 -177.

AMA Style

Kenneth J. Rodgers, Brendan Main, Kate Samardzic. Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity. Neurotoxicity Research. 2017; 33 (1):168-177.

Chicago/Turabian Style

Kenneth J. Rodgers; Brendan Main; Kate Samardzic. 2017. "Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity." Neurotoxicity Research 33, no. 1: 168-177.

Book chapter
Published: 21 March 2017 in Toxins and Drug Discovery
Reads 0
Downloads 0

The 20 DNA-coded protein amino acids play central roles in the metabolism of most organisms. As well as being the building blocks for proteins, they play essential roles in a diverse range of metabolic pathways. They are estimated to be around 1000 molecules in nature, which share the same basic structure as these organic amino acids consisting of an α-carbon attached to a carboxyl group, an amino group, a hydrogen atom, and a unique side-chain group. Many “nonprotein” amino acids (NPAAs) are plant secondary metabolites. In this chapter, the authors discuss plant NPAAs that have a similar chemical structure, size, shape, and charge to protein amino acids and can be mistakenly used in protein synthesis, interfere in biochemical pathways, overstimulate receptors, or chelate metal ions. Most often this results in some level of toxicity to the target organism and can confer some advantage to the plant. Toxic NPAAs might have evolved as defense chemicals that can be released into the soil to inhibit the growth of other plants or agents that can limit insect herbivory. The effects of NPAAs on human health are not well understood. Consumption of a number of plants that contain NPAAs has been shown to have acutely toxic effects in humans. The key questions that remain unanswered are to what extent can NPAAs enter the food chain and what are the effects of a chronic low-level exposure to toxic plant NPAAs?

ACS Style

Kenneth J. Rodgers; Kate Samardzic; Brendan J. Main. Toxic Nonprotein Amino Acids. Toxins and Drug Discovery 2017, 263 -285.

AMA Style

Kenneth J. Rodgers, Kate Samardzic, Brendan J. Main. Toxic Nonprotein Amino Acids. Toxins and Drug Discovery. 2017; ():263-285.

Chicago/Turabian Style

Kenneth J. Rodgers; Kate Samardzic; Brendan J. Main. 2017. "Toxic Nonprotein Amino Acids." Toxins and Drug Discovery , no. : 263-285.

Conference paper
Published: 01 March 2017 in INTED2017 Proceedings
Reads 0
Downloads 0
ACS Style

J. Reyna; P. Meier; J. Hanham; P. Vlachopoulos; Kenneth Rodgers. LEARNER-GENERATED DIGITAL MEDIA (LGDM) FRAMEWORK. INTED2017 Proceedings 2017, 1, 8777 -8781.

AMA Style

J. Reyna, P. Meier, J. Hanham, P. Vlachopoulos, Kenneth Rodgers. LEARNER-GENERATED DIGITAL MEDIA (LGDM) FRAMEWORK. INTED2017 Proceedings. 2017; 1 ():8777-8781.

Chicago/Turabian Style

J. Reyna; P. Meier; J. Hanham; P. Vlachopoulos; Kenneth Rodgers. 2017. "LEARNER-GENERATED DIGITAL MEDIA (LGDM) FRAMEWORK." INTED2017 Proceedings 1, no. : 8777-8781.

Journal article
Published: 07 May 2016 in Atherosclerosis
Reads 0
Downloads 0

ApoA-IV treatment is associated with a more stable plaque phenotype and a reduced incidence of acute disruptions in this mouse model.

ACS Style

F.R.B. Geronimo; P.J. Barter; K.A. Rye; A.K. Heather; K.D. Shearston; K.J. Rodgers. Plaque stabilizing effects of apolipoprotein A-IV. Atherosclerosis 2016, 251, 39 -46.

AMA Style

F.R.B. Geronimo, P.J. Barter, K.A. Rye, A.K. Heather, K.D. Shearston, K.J. Rodgers. Plaque stabilizing effects of apolipoprotein A-IV. Atherosclerosis. 2016; 251 ():39-46.

Chicago/Turabian Style

F.R.B. Geronimo; P.J. Barter; K.A. Rye; A.K. Heather; K.D. Shearston; K.J. Rodgers. 2016. "Plaque stabilizing effects of apolipoprotein A-IV." Atherosclerosis 251, no. : 39-46.

Journal article
Published: 01 January 2016 in Toxicon
Reads 0
Downloads 0

β-methylamino-L-alanine (BMAA), a non-protein amino acid synthesised by cyanobacteria, has been linked to a complex neurological disorder on Guam and more recently to other cases of sporadic ALS (sALS), however the mechanisms of BMAA toxicity are not completely understood. We have previously demonstrated that BMAA is misincorporated into newly synthesised proteins by human neuroblastoma cells and fibroblasts, resulting in the formation of autofluorescent material and the induction of apoptotic cell death. In the present study we show that BMAA at low levels does not cause an acute toxicity in neuroblastoma cells but increases the expression of the ER stress marker, C/EBP homologous protein (CHOP) and increases the activity of the pro-apoptotic enzyme caspase-3. We also observed an increase in the activity of the lysosomal cysteine proteases cathepsin B and L, characteristic of the accumulation of proteins in the lysosomal system. We were able to prevent these proteotoxic effects in neuroblastoma cells through co-treatment with l-serine suggesting that they resulted from incorporation of BMAA into proteins. Misincorporation provides a possible mechanism whereby BMAA could initiate misfolding, and the accumulation of aggregate-prone proteins in neurons. This build-up of misfolded proteins could explain the long latency period of the disease previously reported on Guam.

ACS Style

Brendan J. Main; Rachael A. Dunlop; Kenneth J. Rodgers. The use of l-serine to prevent β-methylamino-l-alanine (BMAA)-induced proteotoxic stress in vitro. Toxicon 2016, 109, 7 -12.

AMA Style

Brendan J. Main, Rachael A. Dunlop, Kenneth J. Rodgers. The use of l-serine to prevent β-methylamino-l-alanine (BMAA)-induced proteotoxic stress in vitro. Toxicon. 2016; 109 ():7-12.

Chicago/Turabian Style

Brendan J. Main; Rachael A. Dunlop; Kenneth J. Rodgers. 2016. "The use of l-serine to prevent β-methylamino-l-alanine (BMAA)-induced proteotoxic stress in vitro." Toxicon 109, no. : 7-12.

Journal article
Published: 01 November 2015 in Biochimica et Biophysica Acta (BBA) - General Subjects
Reads 0
Downloads 0

The accumulation of oxidised proteins in ageing cells and tissues results from an increase in oxidant damage coupled with impaired degradation of the damaged proteins. Heat Shock Proteins (HSP) and other chaperones are required to recognise damaged proteins and transport them to the lysosomal and proteasomal degradation pathways. How these systems fail in ageing cells is not clear. We monitor oxidised protein accumulation, the activity of the proteasome and lysosomal proteases, and HSP levels in MRC-5 fibroblasts throughout their mitotic lifespan. We then use a novel in vitro cell culture model to experimentally generate oxidised proteins in young and old MRC-5 fibroblasts and compare their rates of degradation and changes in the key pathways involved in oxidised protein removal. We show that the activity of the proteasome and some lysosomal enzymes decreases with ageing in MRC-5 cells as do levels of HSP70 but this is not associated with an accumulation of oxidised proteins which only occurs as cells closely approach post-mitotic senescence. Old cells are unable to degrade experimentally generated oxidised proteins as efficiently as young cells. Exposure to mild heat stress however increases the efficiency of oxidised protein degradation by young cells and increases levels of HSP70. Our results highlight the importance of the HSP/chaperone system in oxidised protein metabolism, particularly in ageing cells. These data might have implications for the development of therapies for pathologies associated with protein accumulation and suggest that the HSP/chaperone system would be an important target.

ACS Style

Nae Shiozawa-West; Rachael A. Dunlop; Kenneth J. Rodgers. Using an in vitro model to study oxidised protein accumulation in ageing fibroblasts. Biochimica et Biophysica Acta (BBA) - General Subjects 2015, 1850, 2177 -2184.

AMA Style

Nae Shiozawa-West, Rachael A. Dunlop, Kenneth J. Rodgers. Using an in vitro model to study oxidised protein accumulation in ageing fibroblasts. Biochimica et Biophysica Acta (BBA) - General Subjects. 2015; 1850 (11):2177-2184.

Chicago/Turabian Style

Nae Shiozawa-West; Rachael A. Dunlop; Kenneth J. Rodgers. 2015. "Using an in vitro model to study oxidised protein accumulation in ageing fibroblasts." Biochimica et Biophysica Acta (BBA) - General Subjects 1850, no. 11: 2177-2184.