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Hypoxia Triggers Subcellular Compartmental Redox Signaling in Vascular Smooth Muscle Cells

Hypoxia Triggers Subcellular Compartmental Redox Signaling in Vascular Smooth Muscle Cells Hypoxia Triggers Subcellular Compartmental Redox Signaling in Vascular Smooth Muscle Cells Gregory B. Waypa, Jeremy D. Marks, Robert Guzy, Paul T. Mungai, Jacqueline Schriewer, Danijela Dokic, Paul T. Schumacker Rationale: Recent studies have implicated mitochondrial reactive oxygen species (ROS) in regulating hypoxic pulmonary vasoconstriction (HPV), but controversy exists regarding whether hypoxia increases or decreases ROS generation. Objective: This study tested the hypothesis that hypoxia induces redox changes that differ among subcellular compartments in pulmonary (PASMCs) and systemic (SASMCs) smooth muscle cells. Methods and Results: We used a novel, redox-sensitive, ratiometric fluorescent protein sensor (RoGFP) to assess the effects of hypoxia on redox signaling in cultured PASMCs and SASMCs. Using genetic targeting sequences, RoGFP was expressed in the cytosol (Cyto-RoGFP), the mitochondrial matrix (Mito-RoGFP), or the mitochon- drial intermembrane space (IMS-RoGFP), allowing assessment of oxidant signaling in distinct intracellular compartments. Superfusion of PASMCs or SASMCs with hypoxic media increased oxidation of both Cyto- RoGFP and IMS-RoGFP. However, hypoxia decreased oxidation of Mito-RoGFP in both cell types. The hypoxia-induced oxidation of Cyto-RoGFP was attenuated through the overexpression of cytosolic catalase in PASMCs. Conclusions: These results indicate that hypoxia causes a decrease in nonspecific ROS generation in the matrix compartment, whereas it http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Circulation Research Wolters Kluwer Health

Hypoxia Triggers Subcellular Compartmental Redox Signaling in Vascular Smooth Muscle Cells

Schumacker, Paul T.
Circulation Research , Volume 106 (3) – Feb 1, 2010
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References (60)

ISSN
0009-7330
eISSN
1524-4571
DOI
10.1161/CIRCRESAHA.109.206334
pmid
20019331
Publisher site
See Article on Publisher Site

Abstract

Hypoxia Triggers Subcellular Compartmental Redox Signaling in Vascular Smooth Muscle Cells Gregory B. Waypa, Jeremy D. Marks, Robert Guzy, Paul T. Mungai, Jacqueline Schriewer, Danijela Dokic, Paul T. Schumacker Rationale: Recent studies have implicated mitochondrial reactive oxygen species (ROS) in regulating hypoxic pulmonary vasoconstriction (HPV), but controversy exists regarding whether hypoxia increases or decreases ROS generation. Objective: This study tested the hypothesis that hypoxia induces redox changes that differ among subcellular compartments in pulmonary (PASMCs) and systemic (SASMCs) smooth muscle cells. Methods and Results: We used a novel, redox-sensitive, ratiometric fluorescent protein sensor (RoGFP) to assess the effects of hypoxia on redox signaling in cultured PASMCs and SASMCs. Using genetic targeting sequences, RoGFP was expressed in the cytosol (Cyto-RoGFP), the mitochondrial matrix (Mito-RoGFP), or the mitochon- drial intermembrane space (IMS-RoGFP), allowing assessment of oxidant signaling in distinct intracellular compartments. Superfusion of PASMCs or SASMCs with hypoxic media increased oxidation of both Cyto- RoGFP and IMS-RoGFP. However, hypoxia decreased oxidation of Mito-RoGFP in both cell types. The hypoxia-induced oxidation of Cyto-RoGFP was attenuated through the overexpression of cytosolic catalase in PASMCs. Conclusions: These results indicate that hypoxia causes a decrease in nonspecific ROS generation in the matrix compartment, whereas it

Journal

Circulation Research – Wolters Kluwer Health

Published: Feb 1, 2010

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