Protopine regulates oxidative stress, apoptosis and autophagy in H9C2 cardiomyocytes under hypoxic conditions

The heart is highly sensitive to oxygen deprivation, and hypoxia can lead to cardiomyocyte damage and subsequent cardiac dysfunction. Protopine Pro), an isoquinoline alkaloid derived from various herbs, exhibits diverse biological activities. However, the protective mechanisms of Pro against hypoxia-induced cardiomyocyte damage are not well understood. In this study, Pro was observed to stimulate cell proliferation in H9C2 cardiomyocytes under hypoxia/reoxygenation (H/R) conditions and mitigate apoptosis typically associated with H/R exposure. Despite a notable increase in oxidative stress following H/R treatment, Pro treatment effectively reduced this effect. Additionally, Pro was found to enhance autophagy in H/R-treated H9C2 cells, as evidenced by higher microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I ratios and increased LC3B fluorescence intensity. The activation of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by Pro was also demonstrated. Overall, Pro influences oxidative stress, apoptosis, and autophagy in H9C2 cardiomyocytes under H/R conditions by activating the PTEN/PI3K/Akt pathway, suggesting it as a promising agent to mitigate hypoxia-induced cardiomyocyte damage.

Protopine; H9C2 cardiomyocytes; Hypoxia; Autophagy; PTEN/PI3K/Akt pathway

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