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.