BACKGROUND: Reperfusion therapy is widely utilized for acute myocardial infarction (AMI), so ischemia/reperfusion (I/R) of the heart is frequently encountered in clinical practice. The curative effects of reperfusion therapy for AMI are favourable in most cases, but reperfusion can also cause harmful effect to cardiomyocytes. Hydroxysafflor yellow A (HSYA) is an effective therapeutic agent to alleviate I/R injury, but the mechanisms underlying this therapeutic effect are unknown. METHODS AND RESULTS: The H9c2 cardiomyocyte cell line was incubated with or without HSYA during hypoxia, then it was reoxygenated. In the presence of HSYA, reoxygenation resulted in the upregulated expression and activity of heme oxygenase-1 (HO-1), phosphorylation of Akt, translocation of nuclear factor Nrf2, and most importantly, a reduction in A/R-induced apoptosis. An HO-1 inhibitor completely suppressed HO-1 enzymatic activity upregulated by HSYA and notably diminished the anti-apoptotic effect of HSYA. An inhibitor of PI3K, completely blocked Akt phosphorylation induced by HSYA and partly negated HSYA-induced upregulation of HO-1, translocation of nuclear factor Nrf2 and suppression of apoptosis in the H9c2 cardiomyocytes. CONCLUSIONS: Our study suggests that HSYA can provide protection to H9c2 cardiomyocytes against A/R-induced apoptosis. This protective effect largely depends on the upregulation of HO-1 expression through the PI3K/Akt/Nrf2 signaling pathway.
BACKGROUND: Reperfusion therapy is widely utilized for acute myocardial infarction (AMI), so ischemia/reperfusion (I/R) of the heart is frequently encountered in clinical practice. The curative effects of reperfusion therapy for AMI are favourable in most cases, but reperfusion can also cause harmful effect to cardiomyocytes. Hydroxysafflor yellow A (HSYA) is an effective therapeutic agent to alleviate I/R injury, but the mechanisms underlying this therapeutic effect are unknown. METHODS AND RESULTS: The H9c2 cardiomyocyte cell line was incubated with or without HSYA during hypoxia, then it was reoxygenated. In the presence of HSYA, reoxygenation resulted in the upregulated expression and activity of heme oxygenase-1 (HO-1), phosphorylation of Akt, translocation of nuclear factor Nrf2, and most importantly, a reduction in A/R-induced apoptosis. An HO-1 inhibitor completely suppressed HO-1 enzymatic activity upregulated by HSYA and notably diminished the anti-apoptotic effect of HSYA. An inhibitor of PI3K, completely blocked Akt phosphorylation induced by HSYA and partly negated HSYA-induced upregulation of HO-1, translocation of nuclear factor Nrf2 and suppression of apoptosis in the H9c2 cardiomyocytes. CONCLUSIONS: Our study suggests that HSYA can provide protection to H9c2 cardiomyocytes against A/R-induced apoptosis. This protective effect largely depends on the upregulation of HO-1 expression through the PI3K/Akt/Nrf2 signaling pathway.
Authors: S Der Sarkissian; J-F Cailhier; M Borie; L-M Stevens; L Gaboury; S Mansour; P Hamet; N Noiseux Journal: Br J Pharmacol Date: 2014-12 Impact factor: 8.739