Palmitic acid, but not high-glucose, induced myocardial apoptosis is alleviated by N‑acetylcysteine due to attenuated mitochondrial-derived ROS accumulation-induced endoplasmic reticulum stress

Cell Death & Disease
Yang HeWei-Jin Fang

Abstract

Pharmacological inhibition of reactive oxygen species (ROS) is a potential strategy to prevent diabetes-induced cardiac dysfunction. This study was designed to investigate precise effects of antioxidant N‑acetylcysteine (NAC) in alleviating diabetic cardiomyopathy (DCM). Echocardiography and histologic studies were performed 12 weeks after streptozocin injection. Protein levels involved in endoplasmic reticulum stress (ERS) and apoptosis were analyzed by western blotting in diabetic hearts or high-glucose (HG, 30 mM)- and palmitic acid (PA, 300 μM)-cultured neonatal rat cardiomyocytes (NRCMs). ROS generation and structural alterations of mitochondria were also assessed. We report that NAC alleviated diabetes-induced cardiac abnormality, including restored ejection fraction (EF %), fraction shortening (FS %), peak E to peak A ratio (E/A) and reduced cardiac hypertrophy and fibrosis. These effects were concomitant with blocked ERS and apoptosis, as evidenced by inactivation of phosphorylated inositol-requiring enzyme-1α (IRE1α)/spliced X-box binding protein 1 (XBP1), phosphorylated protein kinase-like kinase (PERK)/phosphorylated eukaryotic initiation factor 2α (eIF2α) and glucose-regulated protein 78 (GRP78)/activating transcrip...Continue Reading

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Citations

Jul 17, 2019·Apoptosis : an International Journal on Programmed Cell Death·Juan Ignacio BurgosMartin Vila Petroff
Jan 23, 2020·Cancer Biotherapy & Radiopharmaceuticals·Hongwei LiRui Zhang
Sep 17, 2020·In Vitro Cellular & Developmental Biology. Animal·Borui LiDewei Zhao
Jul 4, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peng LiJianbin He
May 16, 2019·Oxidative Medicine and Cellular Longevity·Shengbin HuangYihuai Pan
Dec 22, 2020·European Journal of Pharmacology·Xuesheng PanYan Huang
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Namrita KaurWei Liu
Nov 6, 2020·In Vitro Cellular & Developmental Biology. Animal·Hui PeiZhiqiang Zhu
Sep 15, 2021·Cardiovascular Drugs and Therapy·Xinghua PeiWu Lu

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Methods Mentioned

BETA
flow cytometry
transmission electron microscopy
protein assay
PCR
electrophoresis

Software Mentioned

ImageJ
Operetta®

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