N-Acetylcysteine Alleviates Phenylephrine-Induced Cardiomyocyte Dysfunction via Engaging PI3K/AKT Signaling Pathway

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Reactive oxygen species (ROS) and oxidative stress contribute to cardiomyocyte hypertrophy and apoptosis, key factors in heart failure pathogenesis.
• Understanding the role of antioxidants in mitigating these cellular dysfunctions is critical for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the protective effects of the antioxidant N-acetylcysteine (NAC) against cardiomyocyte dysfunction.
• To elucidate the molecular mechanisms underlying NAC's action, particularly its impact on oxidative stress and signaling pathways.

Main Methods:

• Primary cultured neonatal rat cardiomyocytes (NRCMs) were treated with phenylephrine to induce dysfunction.
• N-acetylcysteine (NAC) was administered to assess its effects on cell size, hypertrophic/fibrotic/apoptotic markers, and ROS levels.
• Gene and protein expression (RT-PCR, Western blot), antioxidant enzyme activities (T-AOC, GSH-Px, SOD), and PI3K/AKT signaling pathway activation were analyzed.

Main Results:

• NAC significantly inhibited phenylephrine-induced cardiomyocyte hypertrophy, fibrosis, and apoptosis.
• NAC treatment attenuated elevated ROS levels and enhanced the activity of antioxidant enzymes (T-AOC, GSH-Px, SOD).
• NAC increased the protein expression of phosphorylated PI3K and AKT, indicating activation of the PI3K/AKT signaling pathway, which was confirmed to mediate NAC's protective effects.

Conclusions:

• N-acetylcysteine (NAC) effectively attenuates cardiomyocyte dysfunction induced by phenylephrine.
• NAC exerts its protective effects, at least partially, by modulating the ROS-mediated PI3K/AKT signaling pathway.
• These findings highlight NAC's potential as a therapeutic agent for heart failure by combating oxidative stress and regulating key survival pathways.