Interaction of endothelial nitric oxide synthase with mitochondria regulates oxidative stress and function in fetal pulmonary artery endothelial cells

American Journal of Physiology. Lung Cellular and Molecular Physiology
G Ganesh KonduriRu-Jeng Teng

Abstract

An increase in oxygen tension at birth is one of the key signals that initiate pulmonary vasodilation in the fetal lung. We investigated the hypothesis that targeting endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane regulates reactive oxygen species (ROS) formation in the fetal pulmonary artery endothelial cells (PAEC) during this transition. We isolated PAEC and pulmonary arteries from 137-day gestation fetal lambs (term = 144 days). We exposed PAEC to a simulated transition from fetal to (3% O2) to normoxic (21%) or hyperoxic (95% O2) postnatal Po2 or to the nitric oxide synthase (NOS) agonist ATP. We assessed the effect of O2 and ATP on eNOS interactions with the mitochondrial outer membrane protein porin and with the chaperone hsp90. We also investigated the effect of decoy peptides that blocked eNOS interactions with porin or hsp90 on PAEC angiogenesis and vasodilator function of pulmonary arteries. Transition of fetal PAEC from 3 to 21% O2 but not to 95% O2 or exposure to ATP increased eNOS association with hsp90 and porin. Decoy peptides that blocked eNOS interactions decreased NO release, increased O2 consumption and mitochondrial ROS levels, and impaired PAEC angiogenesis. Decoy peptides als...Continue Reading

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Citations

May 3, 2018·Physiological Reviews·Charles A DucsayLubo Zhang
Feb 18, 2018·Fundamental & Clinical Pharmacology·Nair AnupamaKozhiparambil Gopalan Raghu
Jan 19, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jeffrey D MarshallPatty J Lee
Feb 13, 2020·American Journal of Respiratory Cell and Molecular Biology·Ujala RanaGirija G Konduri
Apr 8, 2020·Canadian Respiratory Journal : Journal of the Canadian Thoracic Society·Juwhan ChoiKyung Hoon Min
Aug 11, 2019·Redox Biology·Lixiao ZhangHong Wang

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