title: Iptakalim protects PC12 cell against H2O2-induced oxidative injury via opening mitochondrial ATP-sensitive potassium channel.
abstract: The final common pathway in the demise of dopaminergic neurons in Parkinson's disease may involve oxidative stress and excitotoxicity. In this study, we examined the neuroprotective effects of a novel ATP-sensitive potassium channel (K(ATP)) opener, iptakalim (IPT), against H(2)O(2)-induced cytotoxicity in rat dopaminergic PC12 cells. Pretreatment with IPT could attenuate increased extracellular glutamate levels and inhibit calcium influxing induced by H(2)O(2). Moreover, IPT regulated the expressions of bcl-2 and bax which were responsible for inhibiting apoptosis in PC12 cells. These protective effects of IPT were abolished by selective mitoK(ATP) channel blocker 5-hydroxydecanoate. Therefore, IPT can protect PC12 cells against H(2)O(2)-induced oxidative injury via activating mitoK(ATP) channel.
authors.affiliation: Laboratory of Neuropharmacology, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chai
authors.forename: Ling
authors.initials: L
authors.lastname: Niu
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Sun
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D016716:PC12 Cells; D015221:Potassium Channels / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats
chemical_list: D024101:Mitochondrial Proteins; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D018696:Neuroprotective Agents; D015221:Potassium Channels; D011437:Propylamines; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D003981:Diazoxide; D002118:Calcium