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Mitochondrial rieske protein, are you a real hypoxic sensor in pulmonary artery smooth muscle cells?
Author(s) -
Korde Amit S,
Wang YongXiao
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1174.2
Subject(s) - hypoxic pulmonary vasoconstriction , hypoxia (environmental) , pulmonary artery , mitochondrial ros , microbiology and biotechnology , mitochondrion , gene knockdown , reactive oxygen species , stimulation , small interfering rna , chemistry , biology , medicine , endocrinology , oxygen , biochemistry , rna , apoptosis , gene , organic chemistry
It is well established that hypoxia causes vasoconstriction in pulmonary arteries (HPV), which serves as an important physiological mechanism to preserve the sufficient matching of regional alveolar ventilation and pulmonary, but may also result in pulmonary hypertension when alveolar hypoxia becomes global. While the molecular mechanisms underlying HPV are incompletely understood, there is extensive evidence to indicate that mitochondria are involved in hypoxic sensing to mediate hypoxic cellular responses in pulmonary artery smooth muscle cells (PASMCs). In this study, we have found the activity of isolated mitochondrial complex III from mouse pulmonary arteries is significantly increased during hypoxic stimulation. Hypoxia results in a large increase in reactive oxygen species (ROS) generation as well in isolated mitochondrial complex III. Rieske protein knockdown by siRNAs blocks hypoxia‐induced increase in the activity and ROS formation of isolated mitochondrial complex III from mouse PASMCs, while gene overexpression of rieske protein produces an opposite effect. Interestingly, we have also shown that the iron chelator desferrioxamine blocks hypoxic increase in the activity and ROS formation of isolated complex III from mouse pulmonary arteries. Overall, our data indicate that mitochondrial complex III rieske protein may function as a major hypoxic sensor to affect ROS generation leading to hypoxic cellular responses in PASMCs.