title: Luteolin protects osteoblastic MC3T3-E1 cells from antimycin A-induced cytotoxicity through the improved mitochondrial function and activation of PI3K/Akt/CREB.
abstract: Luteolin is a flavonoid found in many herbal extracts including celery, green pepper, parsley, perilla leaf and seeds, and chamomile. Antimycin A (AMA) is an inhibitor of the mitochondrial electron transport chain. In the present study, the protective effect of luteolin on AMA-induced cell damage was investigated in osteoblastic MC3T3-E1 cells. Luteolin significantly increased the viability of MC3T3-E1 cells in the presence of AMA and the effect of luteolin in increasing cell viability was completely prevented by the presence of LY294002, Akt inhibitor, or auranofin, suggesting that the effect of luteolin might be partly mediated from PI3K, Akt, and thioredoxin reductase. Pre-treatment with luteolin prior to AMA exposure significantly prevented mitochondrial membrane potential dissipation, ATP loss, inactivation of complex I and IV, ROS production, inactivation of thioredoxin reductase, intracellular calcium elevation, and cytochrome c release induced by AMA. Moreover, luteolin increased activities of PI3K (phosphoinositide 3-kinase) and Akt (protein kinase B), and CREB (cAMP-response element-binding protein) phosphorylation inhibited by AMA treatment. Collectively, these results suggest that luteolin protects MC3T3-E1 cells from AMA-induced cell damage through the improved mitochondrial function and activation of PI3K/Akt/CREB.
authors.affiliation: Department of Food and Nutrition, Education Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. cheunmi@hanmail.net
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009249:NADP / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D002308:Cardiolipins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D020011:Protective Agents; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D009249:NADP; D000968:Antimycin A; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D013880:Thioredoxin-Disulfide Reductase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D047311:Luteolin; D002118:Calcium