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Rieske Iron‐Sulfur Protein in Mitochondrial Complex III Is Essential for the Heterogeneity of Hypoxic Cellular Responses in Pulmonary and Systemic (Mesenteric) Artery Smooth Muscle Cells
Author(s) -
Wang YongXiao,
Korde Amit,
Yadav Vishal,
Zheng YunMin
Publication year - 2015
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.29.1_supplement.859.1
Subject(s) - hypoxic pulmonary vasoconstriction , hypoxia (environmental) , reactive oxygen species , chemistry , contraction (grammar) , mitochondrion , microbiology and biotechnology , mesenteric arteries , vascular smooth muscle , mitochondrial ros , pulmonary artery , vasoconstriction , medicine , pharmacology , endocrinology , artery , oxygen , biology , biochemistry , smooth muscle , organic chemistry
Hypoxia is well known to cause pulmonary vasoconstriction, but usually does not induce systemic (e.g., mesenteric) vasoconstriction. The molecular mechanisms responsible for the heterogeneous hypoxic responses in these two different vascular systems remain unclear. Herein we provide the data showing that mRNA and protein expression levels of Rieske iron‐sulfur protein (RISP) in mitochondrial complex III are significantly higher in pulmonary artery smooth muscle cells (PASMCs) than in mesenteric artery SMCs (MASMCs). Exposure of acute hypoxia for 5 min causes a large increase in reactive oxygen species (ROS) generation in isolated PASM, but not in MASM, cells, mitochondria and complex III. Acute hypoxia induces a large increase in [Ca 2+ ] i in PASMCs and contraction in PAs, and has no effect in MASMCs. Exogenous H 2 O 2 results in an equivalent increase in [Ca 2+ ] i and contraction in PASMCs and MASMCs. RISP overexpression enables hypoxia to increase ROS generation in MASM cells, mitochondria and complex III, elevate [Ca 2+ ] i in MASMCs and cause contraction in MAs. RISP expression levels are highly correlated with heterogeneous hypoxia‐induced ROS formation, increase in [Ca 2+ ] i and contraction in conduit and resistance PASMCs. RISP silencing blocks, while RISP overexpression augments, the hypoxic ROS, Ca 2+ and contractile responses in conduit and resistance PASMCs. Taken together, our findings for the first time demonstrate that RISP in mitochondrial complex III plays an essential role in heterogeneous hypoxia‐induced ROS, Ca 2+ and contractile responses in pulmonary and systemic (mesenteric) artery SMCs.