title: Possible involvement of transient receptor potential channels in electrophile-induced insulin secretion from RINm5F cells.
abstract: Endogenously produced reactive oxygen species reportedly stimulate insulin secretion from islet β-cells. However, the molecular machinery that governs the oxidant-induced insulin secretion has yet to be determined. The present study demonstrates, using rat islet β-cell-derived RINm5F cells, the involvement of the transient receptor potential (TRP) cation channels in the insulin secretion induced by the lipid peroxidation product 4-hydroxy-2-nonenal. Short-term (1 h) exposure of 4-hydroxy-2-nonenal induced a transient increase in intracellular Ca(2+) concentration and subsequent insulin secretion in a concentration-dependent manner. The increase in intracellular Ca(2+) concentration seemed to be due to an influx through the L-type voltage-dependent Ca(2+) channel, since it was not observed when extracellular Ca(2+) was absent and was inhibited almost completely by diltiazem or nifedipine. Ruthenium red, a non-specific inhibitor of TRP channels, inhibited the Ca(2+) influx and insulin secretion evoked by 4-hydroxy-2-nonenal. Among the TRP channels, TRPA1 was found to be predominantly expressed, not only in RINm5F cells, but also rat islets. TRPA1 agonists, allylisothiocyanate and 15-deoxy-Δ(12,14)-prostaglandin J(2), significantly induced Ca(2+) influx, and a specific inhibitor TRPA1, HC-030031, blocked the effects elicited by 4-hydroxy-2-nonenal. These results suggest that 4-hydroxy-2-nonenal induces Ca(2+) influx via the activation of TRP channels, including TRPA1, which appears to be coupled with the L-type voltage-dependent Ca(2+) channel, and ultimately insulin secretion in RINm5F cells.
authors.affiliation: Department of Biochemical Toxicology, Showa University School of Pharmacy, Tokyo, Japan. numazawa@pharm.showa-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Numazawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Takase
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ahiko
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Takemi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D004110:Diltiazem / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D017953:Isocyanates / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: C477819:15-deoxyprostaglandin J2; D000447:Aldehydes; D000498:Allyl Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D017953:Isocyanates; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C480976:Trpa1 protein, rat; C491149:allyl isocyanate; D004110:Diltiazem; D009543:Nifedipine; C027576:4-hydroxy-2-nonenal; D015230:Prostaglandin D2; D002118:Calcium