Program

PO1-9-37

Taurine as a novel TRPV1 inhibitor that protects against oxidative stress-induced toxicity in C. elegans and mammalian cells

[Speaker] Masataka Moriuchi:1
[Co-author] Yoshio Nakano:1,2, Mary Ann Suico:1, Hirofumi Kai:1,2, Tsuyoshi Shuto:1
1:Kumamoto Univ, Japan, 2:Health life science: Interdisciplinary and Glocal Oriented, Japan

Background
Taurine is considered as an essential amino acid that has an important role in physiological functions, and has pharmacological effects. However, the mechanism of taurine7s actions is still unclear. Some studies showed that the taurine metabolite N-acyl taurine (NAT) activates TRPV1 channel, but the relationship between taurine and TRPV1 is still unknown. Here, we determined the effect of NAT and taurine on TRPV1-dependent activation of Ca2+ influx.
Method
TRPV (Ca2+ channel) function was assessed in HepG2 cells by measuring Ca2+ influx using Ca2+ indicator (Calcium6). The activation of downstream signaling was analyzed by Western blotting of phosphorylated GSK-3B and p38. Lifespan of C. elegans was assessed by determining the response of C. elegans to platinum wire prodding at the indicated day.
Results
NAT treatment in HepG2 cells increased the TRPV1-dependent Ca2+ influx, while taurine reduced TRPV1 agonist-induced Ca2+ influx. Moreover, NAT also enhanced but taurine inhibited GSK-3B, Acetyl-CoA carboxylase, p38 activation and TRPV1-modulatory pathways, suggesting that NAT and taurine regulate TRPV1 function in the opposite manner. We also examined whether the inhibition of TRPV channel is physiologically beneficial using C. elegans oxidative stress model. Taurine extended the longevity of wild type but not TRPV mutant C. elegans under oxidative stress condition, suggesting that TRPV is critical for the anti-oxidative property of taurine in C. elegans. To reveal the importance of taurine-TRPV1 pathway, whole gene expression in taurine-treated C. elegans was investigated by microarray analysis. We found that cAMP-regulated transcriptional co-activators (CRTCs) are important transcriptional factors (TF) for TRPV1 activation that regulate the longevity of C. elegans and mouse as revealed by using TF analysis in Network Analysis. Taurine extended the longevity of wild type but not CRTC mutant C. elegans, suggesting that taurine increases the longevity of C. elegans through TRPV1-CRTC1 pathway.
Conclusion
Our study provides important information on how taurine exerts its pleiotropic effects and demonstrate the possible therapeutic application of taurine as a TRPV1 inhibitor.
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