N-acetylcysteine alleviates H2O2-induced damage via regulating the redox status of intracellular antioxidants in H9c2 cells

作者：Liu, Xiehong; Wang, Li; Cai, Jiaodi; Liu, Ke; Liu, Meidong; Wang, Hao; Zhang, Huali^*

来源：International Journal of Molecular Medicine, 2019, 43(1): 199-208.

DOI：10.3892/ijmm.2018.3962

• oxidative stress
• redox state
• N-acetylcysteine
• thioredoxin 1
• peroxiredoxin 1
• glutathione reductase

N-acetylcysteine (NAC) is a thiol-containing antioxidant that modulates the intracellular redox state. NAC can scavenge reactive oxygen species (ROS) and maintain reduced glutathione (GSH) levels, in order to protect cardiomyocytes from oxidative stress. The present study aimed to determine whether NAC protects cardiomyocytes from oxidative damage by regulating the redox status of intracellular antioxidant proteins. The results revealed that NAC pretreatment increased cell viability and inhibited the activation of caspase-3, -8 and -9 during hydrogen peroxide (H2O2)-induced oxidative stress in H9c2 cells. Furthermore, decreased ROS levels, and increased total and reduced GSH levels were detected in response to NAC pretreatment. Non-reducing redox western blotting was performed to detect the redox status of intracellular antioxidant proteins, including thioredoxin 1 (Trx1), peroxiredoxin 1 (Prx1), GSH reductase (GSR), and phosphatase and tensin homolog (PTEN). The results revealed that the reduced form of Trx1 was markedly increased, and the oxidized forms of Prx1, GSR and PTEN were decreased following NAC pretreatment. Furthermore, NAC pretreatment decreased H2O2-induced phosphorylation of apoptosis signal-regulating kinase 1, which depends on the redox state of Trx1, and increased H2O2-induced phosphorylation of protein kinase B, which is essential to cell survival. To the best of our knowledge, the present study is the first to reveal that NAC pretreatment may alleviate oxidation of intracellular antioxidant proteins to inhibit oxidative stress-induced cardiomyocyte apoptosis.

• 出版日期2019-1
• 单位中南大学