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Nitrotyrosine impairs mitochondrial function in fetal lamb pulmonary artery endothelial cells. Am J Physiol Cell Physiol 2016 Jan 01;310(1):C80-8

Date

10/23/2015

Pubmed ID

26491046

Pubmed Central ID

PMC4698449

DOI

10.1152/ajpcell.00073.2015

Scopus ID

2-s2.0-84952801937   5 Citations

Abstract

Nitration of both protein-bound and free tyrosine by reactive nitrogen species results in the formation of nitrotyrosine (NT). We previously reported that free NT impairs microtubule polymerization and uncouples endothelial nitric oxide synthase (eNOS) function in pulmonary artery endothelial cells (PAEC). Because microtubules modulate mitochondrial function, we hypothesized that increased NT levels during inflammation and oxidative stress will lead to mitochondrial dysfunction in PAEC. PAEC isolated from fetal lambs were exposed to varying concentrations of free NT. At low concentrations (1-10 μM), NT increased nitration of mitochondrial electron transport chain (ETC) protein subunit complexes I-V and state III oxygen consumption. Higher concentrations of NT (50 μM) caused decreased microtubule acetylation, impaired eNOS interactions with mitochondria, and decreased ETC protein levels. We also observed increases in heat shock protein-90 nitration, mitochondrial superoxide formation, and fragmentation of mitochondria in PAEC. Our data suggest that free NT accumulation may impair microtubule polymerization and exacerbate reactive oxygen species-induced cell damage by causing mitochondrial dysfunction.

Author List

Teng RJ, Wu TJ, Afolayan AJ, Konduri GG

Authors

Adeleye James Afolayan MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tzong-Jin Wu MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylation
Animals
Cells, Cultured
DNA, Mitochondrial
Dose-Response Relationship, Drug
Electron Transport Chain Complex Proteins
Endothelial Cells
Gestational Age
HSP90 Heat-Shock Proteins
Microtubules
Mitochondria
Nitric Oxide Synthase Type III
Oxygen Consumption
Protein Binding
Pulmonary Artery
Sheep
Superoxides
Tyrosine
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75