Endothelin-1 Inhibits Apoptosis of Vascular Smooth Muscle Cells Induced by Nitric Oxide and Serum Deprivation via MAP Kinase Pathway

摘要: Endothelin (ET)-1, an endothelium-derived vasoconstrictor and mitogen, acts as antiapoptotic factor against serum deprivation-induced apoptosis of endothelial cells fibroblasts but enhances some cancer cells. In the present study, we examined whether nitric oxide (NO) ET-1 modulate rat vascular smooth muscle (VSMCs) via mitogen-activated protein (MAP) kinase pathway. Both deprivation NO donors (FK409 SNAP) caused VSMCs, demonstrated by TdT-mediated dUTP-biotin nick end-labeling, appearance fragmented DNA, induction caspase-3 activity. dose-dependently antagonized induced donors. A selective ET(A) receptor antagonist (BQ123) a nonselective ET(A/B) (TAK044), not ET(B) (BQ788), inhibited effect ET-1, indicating that is mediated receptor. activated MAP kinase, whose was FK409. Transfection with unphosphorylated wild-type kinase-1 (MAPKK-1) or its constitutively mutant protected VSMCs Inhibition activity PD98059, specific inhibitor MAPKK-1, transfection dominant-negative MAPKK-1 suggesting involvement in effect. The potent inhibitory on suggests counterbalance between 2 factors contributes to process remodeling determining VSMC survival death, respectively, common