title: Pinacidil protects osteoblastic cells against antimycin A-induced oxidative damage.
abstract: The present study aimed to investigate the protective effect of a non-selective mitochondrial adenosine triphosphate (ATP)-sensitive potassium channel (mito-KATP) opener, pinacidil, on antimycin A-induced oxidative damage in osteoblastic MC3T3-E1 cells. Antimycin A inhibits mitochondrial electron transport by binding to complex III. Osteoblastic MC3T3-E1 cells were treated with antimycin A in the presence or absence of pinacidil and markers of mitochondrial function and oxidative stress were subsequently examined. The effects of pinacidil on the activation of phosphoinositide 3-kinase (PI3K), Akt and cyclic adenosine monophosphate‑responsive element-binding protein (CREB) were also examined. In osteoblastic MC3T3-E1 cells exposed to antimycin A, pinacidil inhibited antimycin A-induced cell death. The protective effects of pinacidil on cell survival were prevented by the addition of LY294002 (a PI3K inhibitor), an Akt inhibitor or auranofin [a thioredoxin reductase (TrxR) inhibitor], but not by KATP channel inhibitor glibenclamide. Pinacidil inhibited antimycin A-induced inactivation of PI3K and Akt as well as phosphorylation of CREB and TrxR. Furthermore, pinacidil prevented antimycin A-induced mitochondrial superoxide release, mitochondrial membrane potential dissipation, reduced ATP synthesis and intracellular [Ca2+] elevation. In conclusion, these results suggested that pinacidil may rescue osteoblastic cells from antimycin A-induced cellular damage, potentially via antioxidant activity and restoration of mitochondrial function, which are mediated in part by the PI3K/Akt/CREB signaling pathway.
authors.affiliation: Department of Food and Nutrition, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Cheongju University, Cheongju, Chungcheong 360-764, Republic of Korea.
authors.forename: Woon Won
authors.initials: WW
authors.lastname: Jung
authors.affiliation: Research Institute of Endocrinology, Kyung Hee University Hospital, Seoul 130-702, Republic of Korea.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017362:Cyclic AMP Response Element-Binding Protein; D020011:Protective Agents; D000968:Antimycin A; D020110:Pinacidil; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt