Endoplasmic Reticulum Ca2+ Release Causes Rieske Iron-Sulfur Protein-mediated Mitochondrial ROS Generation in Pulmonary Artery Smooth Muscle Cells.

Endoplasmic Reticulum Ca2+ Release Causes Rieske Iron-Sulfur Protein-mediated Mitochondrial ROS Generation in Pulmonary Artery Smooth Muscle Cells. Biosci Rep. 2019 Nov 11;: Authors: Dong D, Hao Q, Zhang P, Wang T, Han F, Liang X, Fei Z Abstract Mitochondrial reactive oxygen species (ROS) cause Ca2+ release from the Endoplasmic reticulum (ER) via ryanodine receptors (RyRs) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). Here we tested a novel hypothesis that hypoxia-induced RyR-mediated Ca2+ release may, in turn, promote mitochondrial ROS generation contributing to hypoxic cellular responses in PASMCs. Our data reveal that application of caffeine to elevate intracellular Ca2+ concentration ([Ca2+]i) by activating RyRs results in a significant increase in ROS production in cytosol and mitochondria of PASMCs. Norepinephrine to increase [Ca2+]i due to the opening of inositol 1,4,5-triphosphate receptors (IP3Rs) produces similar effects. Exogenous Ca2+ significantly increases mitochondrial-derived ROS generation as well. Ru360 also inhibits the hypoxic ROS production. The RyR antagonist tetracaine or RyR2 gene knockout (KO) suppresses hypoxia-induced responses as well. Inhibition of mitochondrial Ca2+ uptake with Ru360 eliminates N- and Ca2+-induced responses. RISP KD abolishes the hypoxia-induced ROS production in mitochondria of PASMCs. Rieske iron-sulfur protein ...
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research