title: Melatonin modulates apoptosis and TRPM2 channels in transfected cells activated by oxidative stress.
abstract: Transient receptor potential melastatin-like 2 (TRPM2) is a non-selective Ca(2+) permeable cation channel and is known to be activated by H(2)O(2), one of the most important indicators of intracellular oxidative stress. A neurohormone melatonin may have a modulator role on TRPM2 channels activated by oxidative stress because it is a strong antioxidant. In this study we investigated the effects of melatonin on apoptosis, whole cell currents and Ca(2+) influx arising from TRPM2 channels activated by H(2)O(2). In whole-cell patch clamp experiments, TRPM2 channels in transfected Chinese hamster ovary (CHO) cells were activated by H(2)O(2). However, the currents were inhibited either by intracellular or by extracellular melatonin. When intracellular melatonin was introduced by pipette, TRPM2 channel currents were not activated by H(2)O(2) although H(2)O(2)-induced Ca(2+) gating and release were not blocked 2-aminoethyldiphenyl borate (2-APB). Cytosolic Ca(2+) release was measured by Fura-2 and was higher in H(2)O(2) groups than in control. Melatonin also inhibited apoptosis in the transfected cells. In conclusion, we observed modulator roles of intracellular and extracellular melatonin on Ca(2+) influx and apoptosis through a TRPM2 channel in transfected CHO cells.
authors.affiliation: Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey. omercelik.vm@gmail.com
authors.forename: Omer
authors.initials: O
authors.lastname: Celik
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D051152:Clusterin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014162:Transfection
chemical_list: D000975:Antioxidants; D001896:Boron Compounds; D051152:Clusterin; D016877:Oxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D006861:Hydrogen Peroxide; C109986:2-aminoethoxydiphenyl borate; C022616:thiazolyl blue; D008550:Melatonin; D002118:Calcium