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

Unclaimed
Yuhua Tian
Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, No. 1 Ningde Road, Qingdao 266073, China

Basic Info

Basic Info is private.

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

Research articles
Published: 29 July 2021 in Journal of Biological Chemistry
Reads 0
Downloads 0

Transient Receptor Potential vanilloid 1 (TRPV1) ion channel serves as the detector for noxious temperature above 42°C, pungent chemicals like capsaicin and acidic extracellular pH. This channel has also been shown to function as an ionotropic cannabinoid receptor. Despite the solving of high-resolution three-dimensional structures of TRPV1, how endocannabinoids such as anandamide and N-arachidonoyl dopamine bind to and activate this channel remains largely unknown. Here we employed a combination of patch-clamp recording, site-directed mutagenesis and molecular docking techniques to investigate how the endocannabinoids structurally bind to and open the TRPV1 ion channel. We found that these endocannabinoid ligands bind to the vanilloid binding pocket of TRPV1 in the ‘tail-up, head-down' configuration, similar to capsaicin; however, there is a unique interaction with TRPV1 Y512 residue critical for endocannabinoid activation of TRPV1 channels. These data suggest a differential structural mechanism is involved in TRPV1 activation by endocannabinoids compared to the classic agonist capsaicin.

ACS Style

Yanxin Li; Xiaoying Chen; Yingying Nie; Yuhua Tian; Xian Xiao; Fan Yang. Endocannabinoid activation of the TRPV1 ion channel is distinct from activation by capsaicin. Journal of Biological Chemistry 2021, 297, 1 .

AMA Style

Yanxin Li, Xiaoying Chen, Yingying Nie, Yuhua Tian, Xian Xiao, Fan Yang. Endocannabinoid activation of the TRPV1 ion channel is distinct from activation by capsaicin. Journal of Biological Chemistry. 2021; 297 (3):1.

Chicago/Turabian Style

Yanxin Li; Xiaoying Chen; Yingying Nie; Yuhua Tian; Xian Xiao; Fan Yang. 2021. "Endocannabinoid activation of the TRPV1 ion channel is distinct from activation by capsaicin." Journal of Biological Chemistry 297, no. 3: 1.

Journal article
Published: 19 May 2021 in Journal of Biological Chemistry
Reads 0
Downloads 0

Sensing noxiously high temperatures is crucial for living organisms to avoid heat-induced injury. The TRPV1 channel has long been known as a sensor for noxious heat. However, the mechanism of how this channel is activated by heat remains elusive. Here we found that a series of polyols including sucrose, sorbitol, and hyaluronan significantly elevate the heat activation threshold temperature of TRPV1. The modulatory effects of these polyols were only observed when they were perfused extracellularly. Interestingly, mutation of residues E601 and E649 in the outer pore region of TRPV1 largely abolished the effects of these polyols. We further observed that intraplantar injection of polyols into the hind paws of rats reduced their heat-induced pain response. Our observations not only suggest that the extracellular regions of TRPV1 are critical for the modulation of heat activation by polyols, but also indicate a potential role of polyols in reducing heat-induced pain sensation.

ACS Style

Yingying Nie; Yanxin Li; Lei Liu; Shouyan Ren; Yuhua Tian; Fan Yang. Molecular mechanism underlying modulation of TRPV1 heat activation by polyols. Journal of Biological Chemistry 2021, 297, 100806 .

AMA Style

Yingying Nie, Yanxin Li, Lei Liu, Shouyan Ren, Yuhua Tian, Fan Yang. Molecular mechanism underlying modulation of TRPV1 heat activation by polyols. Journal of Biological Chemistry. 2021; 297 (1):100806.

Chicago/Turabian Style

Yingying Nie; Yanxin Li; Lei Liu; Shouyan Ren; Yuhua Tian; Fan Yang. 2021. "Molecular mechanism underlying modulation of TRPV1 heat activation by polyols." Journal of Biological Chemistry 297, no. 1: 100806.

Journal article
Published: 01 July 2020 in Journal of Biological Chemistry
Reads 0
Downloads 0

The transient receptor potential vanilloid 1 (TRPV1) is a heat-activated cation channel that plays a crucial role in ambient temperature detection and thermal homeostasis. Although several structural features of TRPV1 have been shown to be involved in the heat-induced activation of the gating process, the physiological significance of only a few of these key elements has been evaluated in an evolutionary context. Here, using transient expression in HEK293 cells, electrophysiological recordings, and molecular modeling, we show that the pore turret contains both structural and functional determinants that set the heat activation thresholds of distinct TRPV1 orthologs in mammals whose body temperatures widely fluctuate. We found that TRPV1 from the bat Carollia brevicauda (fbTRPV1) exhibits a lower threshold temperature of channel activation than its human ortholog and that three bat-specific amino acid substitutions located at the pore turret are sufficient to determine this threshold temperature. Furthermore, the structure of the TRPV1 pore turret appears to be of physiological and evolutionary significance for differentiating the heat-activated threshold among species-specific TRPV1 orthologs. These findings support a role of the TRPV1 pore turret in tuning the heat-activated threshold and suggest that its evolution was driven by adaption to specific physiological traits within mammals exposed to variable temperatures.

ACS Style

Guangxu Du; Yuhua Tian; Zhihao Yao; Simon Vu; Jie Zheng; Longhui Chai; Kewei Wang; Shilong Yang. A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds. Journal of Biological Chemistry 2020, 295, 9641 -9649.

AMA Style

Guangxu Du, Yuhua Tian, Zhihao Yao, Simon Vu, Jie Zheng, Longhui Chai, Kewei Wang, Shilong Yang. A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds. Journal of Biological Chemistry. 2020; 295 (28):9641-9649.

Chicago/Turabian Style

Guangxu Du; Yuhua Tian; Zhihao Yao; Simon Vu; Jie Zheng; Longhui Chai; Kewei Wang; Shilong Yang. 2020. "A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds." Journal of Biological Chemistry 295, no. 28: 9641-9649.

Journal article
Published: 22 February 2020 in Toxicon
Reads 0
Downloads 0

The nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor for multiple painful stimuli, hence actively pursued as a target for analgesic drugs. We identified a small peptide toxin RhTx2 from the Chinese red-headed centipede that strongly modulates TRPV1 activities. RhTx2, a 31-amino-acid peptide, is similar to a TRPV1-activating toxin RhTx we have previously discovered but with four extra amino acids at the N terminus. We observed that, like RhTx, RhTx2 activated TRPV1, but RhTx2 rapidly desensitized the channel upon prolonged exposure. Desensitization was achieved by reducing both the open probability and the single-channel conductance. RhTx2 is not only a tool to study the desensitization mechanism of TRPV1, but also a promising starting molecule for developing novel analgesics.

ACS Style

Aiqin Zhu; Aerziguli Aierken; Zhihao Yao; Simon Vu; Yuhua Tian; Jie Zheng; Shilong Yang; Fan Yang. A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel. Toxicon 2020, 178, 41 -49.

AMA Style

Aiqin Zhu, Aerziguli Aierken, Zhihao Yao, Simon Vu, Yuhua Tian, Jie Zheng, Shilong Yang, Fan Yang. A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel. Toxicon. 2020; 178 ():41-49.

Chicago/Turabian Style

Aiqin Zhu; Aerziguli Aierken; Zhihao Yao; Simon Vu; Yuhua Tian; Jie Zheng; Shilong Yang; Fan Yang. 2020. "A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel." Toxicon 178, no. : 41-49.

Journal article
Published: 27 November 2019 in Toxins
Reads 0
Downloads 0

Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our study suggests that TRPV1 serves as a primary nociceptor in caterpillar-induced pain and forms the foundation for elucidating the pain-producing mechanism.

ACS Style

Zhihao Yao; Peter Muiruri Kamau; Yalan Han; Jingmei Hu; Anna Luo; Lei Luo; Jie Zheng; Yuhua Tian; Ren Lai. The Latoia consocia Caterpillar Induces Pain by Targeting Nociceptive Ion Channel TRPV1. Toxins 2019, 11, 695 .

AMA Style

Zhihao Yao, Peter Muiruri Kamau, Yalan Han, Jingmei Hu, Anna Luo, Lei Luo, Jie Zheng, Yuhua Tian, Ren Lai. The Latoia consocia Caterpillar Induces Pain by Targeting Nociceptive Ion Channel TRPV1. Toxins. 2019; 11 (12):695.

Chicago/Turabian Style

Zhihao Yao; Peter Muiruri Kamau; Yalan Han; Jingmei Hu; Anna Luo; Lei Luo; Jie Zheng; Yuhua Tian; Ren Lai. 2019. "The Latoia consocia Caterpillar Induces Pain by Targeting Nociceptive Ion Channel TRPV1." Toxins 11, no. 12: 695.

Research paper
Published: 17 June 2019 in Journal of Cerebral Blood Flow & Metabolism
Reads 0
Downloads 0

Background and Purpose Like chili peppers, gingers produce pungent stimuli by a group of vanilloid compounds that activate the nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel. How these compounds interact with TRPV1 remains unclear. Experimental Approach We used computational structural modelling, functional tests (electrophysiology and calcium imaging), and mutagenesis to investigate the structural mechanisms underlying ligand–channel interactions. Key Results The potency of three principal pungent compounds from ginger —shogaol, gingerol, and zingerone—depends on the same two residues in the TRPV1 channel that form a hydrogen bond with the chili pepper pungent compound, capsaicin. Computational modelling revealed binding poses of these ginger compounds similar to those of capsaicin, including a “head‐down tail‐up” orientation, two specific hydrogen bonds, and important contributions of van der Waals interactions by the aliphatic tail. Our study also identified a novel horizontal binding pose of zingerone that allows it to directly interact with the channel pore when bound inside the ligand‐binding pocket. These observations offer a molecular level explanation for how unique structures in the ginger compounds affect their channel activation potency. Conclusions and Implications Mechanistic insights into the interactions of ginger compounds and the TRPV1 cation channel should help guide drug discovery efforts to modulate nociception.

ACS Style

Yue Yin; Yawen Dong; Simon Vu; Fan Yang; Vladimir Yarov-Yarovoy; Yuhua Tian; Jie Zheng. Structural mechanisms underlying activation of TRPV1 channels by pungent compounds in gingers. Journal of Cerebral Blood Flow & Metabolism 2019, 176, 3364 -3377.

AMA Style

Yue Yin, Yawen Dong, Simon Vu, Fan Yang, Vladimir Yarov-Yarovoy, Yuhua Tian, Jie Zheng. Structural mechanisms underlying activation of TRPV1 channels by pungent compounds in gingers. Journal of Cerebral Blood Flow & Metabolism. 2019; 176 (17):3364-3377.

Chicago/Turabian Style

Yue Yin; Yawen Dong; Simon Vu; Fan Yang; Vladimir Yarov-Yarovoy; Yuhua Tian; Jie Zheng. 2019. "Structural mechanisms underlying activation of TRPV1 channels by pungent compounds in gingers." Journal of Cerebral Blood Flow & Metabolism 176, no. 17: 3364-3377.

Short communication
Published: 15 June 2019 in Biochemical and Biophysical Research Communications
Reads 0
Downloads 0

Piperine, the principle pungent compound in black peppers, is known to activate the capsaicin receptor TRPV1 ion channel. How piperine interacts with the channel protein, however, remains unclear. Here we show that piperine binds to the same ligand-binding pocket as capsaicin but in different poses. There was no detectable detrimental effect when T551 and E571, two major sites known to form hydrogen bond with capsaicin, were mutated to a hydrophobic amino acid. Computational structural modeling suggested that piperine makes interactions with multiple amino acids within the ligand binding pocket, including T671 on the pore-forming S6 segment. Mutations of this residue could substantially reduce or even eliminate piperine-induced activation, confirming that T671 is an important site. Our results suggest that the bound piperine may directly interact with the pore-forming S6 segment to induce channel opening. These findings help to explain why piperine is a weak agonist, and may guide future efforts to develop novel pharmaceutical reagents targeting TRPV1.

ACS Style

Yawen Dong; Yue Yin; Simon Vu; Fan Yang; Vladimir Yarov-Yarovoy; Yuhua Tian; Jie Zheng. A distinct structural mechanism underlies TRPV1 activation by piperine. Biochemical and Biophysical Research Communications 2019, 516, 365 -372.

AMA Style

Yawen Dong, Yue Yin, Simon Vu, Fan Yang, Vladimir Yarov-Yarovoy, Yuhua Tian, Jie Zheng. A distinct structural mechanism underlies TRPV1 activation by piperine. Biochemical and Biophysical Research Communications. 2019; 516 (2):365-372.

Chicago/Turabian Style

Yawen Dong; Yue Yin; Simon Vu; Fan Yang; Vladimir Yarov-Yarovoy; Yuhua Tian; Jie Zheng. 2019. "A distinct structural mechanism underlies TRPV1 activation by piperine." Biochemical and Biophysical Research Communications 516, no. 2: 365-372.