title: Involvement of PI3K/Akt/CREB and redox changes in mitochondrial defect of osteoblastic MC3T3-E1 cells.
abstract: Antimycin A (AMA) is an inhibitor of mitochondrial electron transport via its binding to complex III. In the present study, the mechanisms involved in AMA-induced cell damage were investigated. Treatment of osteoblastic MC3T3-E1 cells with AMA decreased adenosine 3',5'-cyclic monophosphate (cAMP) level, activities of phosphoinositide 3-kinase (PI3K) and Akt (protein kinase B), and phosphorylated CREB (cAMP-response element-binding protein). To examine whether AMA-induced cell damage involves altered metabolism of pyridine nucleotides, the levels of NAD(+), NADH, NADP(+), and NADPH were measured. Treatment with AMA significantly decreased the levels of NAD(+) and NADPH. Moreover, the activities of aconitase and thioredoxin reductase were decreased by AMA treatment. These results suggest that PI3K/Akt/CREB pathway and pyridine nucleotide (NAD(+) and NADPH) are related to mitochondria function of osteoblasts.
authors.affiliation: Department of Food and Nutrition, 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
authors.forename: Young Soon
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D002374:Catalase / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D005980:Glutathione Reductase / Q000032:analysis; D044949:Kaempferols / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000032:analysis; D009249:NADP / Q000032:analysis; D010006:Osteoblasts / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000968:Antimycin A; D002374:Catalase; D017362:Cyclic AMP Response Element-Binding Protein; D005978:Glutathione; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D044949:Kaempferols; D009243:NAD; D009249:NADP; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; C492004:Creb1 protein, mouse; C006552:kaempferol