Effects of mitochondrial potassium channel and membrane potential on hypoxic human pulmonary artery smooth muscle cells.

Abstract:

:Chronic hypoxia induces proliferation of human pulmonary artery smooth muscle cells (hPASMCs), leading to remodeling and pulmonary hypertension, but the mechanism remains unclear. The present study tested the roles of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) and mitochondrial membrane potential (DeltaPsi(m)) on hPASMCs under normoxic or hypoxic conditions. Our results demonstrated that diazoxide or hypoxia, alone or in combination, could depolarize DeltaPsi(m) through opening mitoK(ATP), release of cytochrome C, and overproduction of hydrogen peroxide by mitochondria, resulting in increased proliferation and decreased apoptosis of hPASMCs. Five-hydroxydecanoate could partly reduce these hypoxia-dependent responses. These results suggest that the opening of mitoK(ATP) followed by a depolarization of DeltaPsi(m) might play an important role in hypoxic proliferation of hPASMCs through cytochrome C accumulation within the mitochondria or mitochondrial overproduction of hydrogen peroxide.

authors

Hu HL,Zhang ZX,Chen CS,Cai C,Zhao JP,Wang X

doi

10.1165/rcmb.2009-0017OC

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

661-6

issue

6

eissn

1044-1549

issn

1535-4989

pii

2009-0017OC

journal_volume

42

pub_type

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