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Nox2 dependent redox-regulation of Akt and ERK1/2 to promote left ventricular hypertrophy in dietary obesity of mice

Bhatti, S. N. and Li, J.-M. (2020) Nox2 dependent redox-regulation of Akt and ERK1/2 to promote left ventricular hypertrophy in dietary obesity of mice. Biochemical and Biophysical Research Communications, 528 (3). pp. 506-513. ISSN 0006-291X

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To link to this item DOI: 10.1016/j.bbrc.2020.05.162

Abstract/Summary

Background A Nox2 containing NADPH oxidase (Nox2) is involved in the global oxidative stress found in dietary obesity and metabolic disorders. However, the effects of high fat diet (HFD) on cardiac Nox2 activation and signaling in left ventricular hypertrophy (LVH) remain unknown. Methods Left ventricular (LV) tissues isolated from C57BL/6J wild-type (WT) and Nox2 knockout (Nox2KO) mice (11 months old, n = 6 per group) after 4 months of HFD treatment were used. Cardiomyocyte sizes were measured digitally on LV cross-sections. The levels of cardiac reactive oxygen species (ROS) production was determined using lucigenin-chemiluminescence and in situ dihydroethidium (DHE) fluorescence. The levels of Nox subunit expression and redox signaling were examined by immunoblotting and immunofluorescence. Results In comparison to WT normal chow diet control hearts, WT HFD hearts had 1.8-fold increases in cardiomyocyte size, a sign of cardiac hypertrophy, and this was accompanied with ≥2-fold increase in the levels of ROS production, Nox2 expression and the phosphorylation of Akt and ERK1/2. Increased ROS production measured in HFD heart homogenates was inhibited to control levels by Tiron (a cell membrane permeable O2•−scavenger), diphenyleneiodonium (DPI, a flavohaemoprotein inhibitor) and Nox2 ds-tat (a Nox2 assembly inhibitor). However, all of these abnormalities were significantly reduced or absent in Nox2KO hearts under the same HFD. Conclusions Nox2 activation in response to dietary obesity and metabolic disorders plays a key role in cardiac oxidative stress, aberrant redox signaling and cardiomyocyte hypertrophy. Knockout of Nox2 protects hearts from oxidative damage associated with obesity and metabolic disorders.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:91056
Publisher:Elsevier

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