Novel Imaging Approaches Provide New Windows to View Subcellular Changes in the Redox State of Smooth Muscle Cells

Abstract

See related articles, pages 526–535 In this issue of Circulation Research , Schumacker and colleagues1 describe the development of novel genetic targeting approaches that record unique information on subcellular changes in the thiol redox state. Ratiometric rhoGFP fluorescence detectors were used to examine hypoxia-induced redox changes in cultured rat pulmonary and systemic (renal) arterial smooth muscle cells. The role and the origins of peroxide contributing to the redox changes were dissected by genetically overexpressing catalase in subcellular compartments. Although the study was designed to provide further insight into the controversial hypothesis that hypoxia promotes contraction of pulmonary arterial smooth muscle by increasing the release of mitochondrial-derived hydrogen peroxide, the methodological approaches used may be viewed as a more important aspect of the work. In particular, the molecular transfection approaches used provide new windows of opportunity to examine the nature of subcellular redox signaling. Overall, the study contained impressive data showing that hypoxia increases the concentration of cytosolic hydrogen peroxide, based on the inhibition of thiol oxidation-dependent fluorescence responses by catalase overexpressed in the cytosol. Hypoxia also increased oxidation in the mitochondrial intermembrane space but, decreased it in the mitochondrial matrix in a manner that was not affected by the overexpression of catalase in the mitochondrial matrix. These results underscore the need …