Modulation of vascular smooth muscle cell growth by magnesium-role of mitogen-activated protein kinases.

摘要: We tested the hypothesis that Mg 2 + influences growth of vascular smooth muscle cells (VSMCs) by modulating cell cycle activation through mitogen-activated protein (MAP) kinase-dependent pathways. Rat VSMCs were grown inculture medium containing normal (1.02 mmol/L, control) and increasing concentrations (2-4 mmol/L) for 1-8 days. Effects varying extracellular concentration ([Mg ] e ) on intracellular free i assessed using mag-fura. Growth actions w ere evaluated measuring activation, DNA synthesis, synthesis. Expression promoters, cyclin D1, E, Cdk2, Cdk4 was immunoblotting. Phosphorylation inhibitors p21 c p 1 p27 k MAP kinases, ERK½, p38MAP kinase, JNK phospho-specific antibodies. [Mg increased in a dose-dependent manner response to . These effects evident within days maximal responses obtained after 6 High induced with lower proportion cel Is G phase (75 ′ 1.0%) higher fraction S (12 0.7%) versus control (G , 88.5 1.4%; S, 6.8 1.2%; P<0.05). This associated content D1 decreased In exposed mmol/L synthesis ∼threefold. MEK½ ERK1/ enhanced two threefold rapid, occurring MEK3/6, p38 unaltered [Mg2] PD98059 (10 - 5 mol/L), specific inhibitor, but not SB202190 mol/L) (specific kinase inhibitor), attenuated -induced actions. data demonstrate novel findings regulation occurs via ERK½-dependent, kinase-independent