Effects of mitochondrial potassium channel and membrane potential on hypoxic human pulmonary artery smooth muscle cells.
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.
Hu
Hong-Ling
HL
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Zhang
Zhen-Xiang
ZX
Chen
Cheng-Shui
CS
Cai
Chang
C
Zhao
Jian-Ping
JP
Wang
Xiangdong
X
D017209:Apoptosis; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006880:Hydroxy Acids / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism
D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D003981:Diazoxide