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Wenxin Granule Ameliorates Hypoxia/Reoxygenation-Induced Oxidative Stress in Mitochondria via the PKC-δ/NOX2/ROS Pathway in H9c2 Cells.
Jin, Qihui; Jiang, Yanhong; Fu, Lizhong; Zheng, Yanqiu; Ding, Yuxia; Liu, Qian.
Afiliação
  • Jin Q; Department of Geriatric Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
  • Jiang Y; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, China.
  • Fu L; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, China.
  • Zheng Y; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, China.
  • Ding Y; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, China.
  • Liu Q; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, China.
Oxid Med Cell Longev ; 2020: 3245483, 2020.
Article em En | MEDLINE | ID: mdl-32566078
ABSTRACT
Myocardial infarction and following reperfusion therapy-induced myocardial ischemia/reperfusion (I/R) injury have been recognized as an important subject of cardiovascular disease with high mortality. As the antiarrhythmic agent, Wenxin Granule (WXG) is widely used to arrhythmia and heart failure. In our pilot study, we found the antioxidative potential of WXG in the treatment of myocardial I/R. This study is aimed at investigating whether WXG could treat cardiomyocyte hypoxia/reoxygenation (H/R) injury by inhibiting oxidative stress in mitochondria. The H9c2 cardiomyocyte cell line was subject to H/R stimuli to mimic I/R injury in vitro. WXG was added to the culture medium 24 h before H/R exposing as pretreatment. Protein kinase C-δ (PKC-δ) inhibitor rottlerin or PKC-δ lentivirus vectors were conducted on H9c2 cells to downregulate or overexpress PKC-δ protein. Then, the cell viability, oxidative stress levels, intracellular and mitochondrial ROS levels, mitochondrial function, and apoptosis index were analyzed. In addition, PKC-δ protein expression in each group was verified by western blot analysis. Compared with the control group, the PKC-δ protein level was significantly increased in the H/R group, which was remarkably improved by WXG or rottlerin. PKC-δ lentivirus vector-mediated PKC-δ overexpression was not reduced by WXG. WXG significantly improved H/R-induced cell injury, lower levels of SOD and GSH/GSSG ratio, higher levels of MDA, intracellular and mitochondrial ROS content, mitochondrial membrane potential and ATP loss, mitochondrial permeability transition pore opening, NOX2 activation, cytochrome C release, Bax/Bcl-2 ratio and cleaved caspase-3 increasing, and cell apoptosis. Similar findings were obtained from rottlerin treatment. However, the protective effects of WXG were abolished by PKC-δ overexpression, indicating that PKC-δ was a potential target of WXG treatment. Our findings demonstrated a novel mechanism by which WXG attenuated oxidative stress and mitochondrial dysfunction of H9c2 cells induced by H/R stimulation via inhibitory regulation of PKC-δ/NOX2/ROS signaling.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxigênio / Medicamentos de Ervas Chinesas / Transdução de Sinais / Espécies Reativas de Oxigênio / Estresse Oxidativo / Proteína Quinase C-delta / NADPH Oxidase 2 / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Oxid Med Cell Longev Assunto da revista: METABOLISMO Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxigênio / Medicamentos de Ervas Chinesas / Transdução de Sinais / Espécies Reativas de Oxigênio / Estresse Oxidativo / Proteína Quinase C-delta / NADPH Oxidase 2 / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Oxid Med Cell Longev Assunto da revista: METABOLISMO Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China