Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1–FoxO1 pathway

Sirtuins, aging, and cardiovascular risks

“…In summary, SIRT1 acts as a cardioprotective molecule that protects from aging and induces resistance against hypertrophic and oxidative stresses, inhibits cardiomyocyte apoptosis, and regulates cardiac energy metabolism (Alcendor et al 2007;Chen et al 2009;Hsu et al 2010;Luo et al 2014). Moreover, the observations reported in this section strengthen the perception that SIRT1 exerts protective effects against cardiovascular aging and age-related CVDs by mediating multiple signalling pathways.…”

“…The protection afforded by IPC is mediated through activation of multiple signalling pathways, in one of this SIRT1 is activated and, in turn, induces deacetylation of lysine residues in various proteins, including p53 (Bolli, 2007;Yamamoto et al 2014). Furthermore, Chen et al (2009) showed that hypoxiainduced apoptosis generated in H9c2 cells in vitro was attenuated by resveratrol acting through SIRT1: the coincubation of resveratrol with a SIRT1 inhibitor abolished the protective effect. Moreover, resveratrol, via its interaction with SIRT1, suppresses the expression of AT1P-induced vasoconstriction (Higuchi et al 2007).…”

Nicotinamide-induced Mitophagy

“…4 Meanwhile, to induce SIRT1 inhibition in vivo, NAM is frequently used at concentrations higher than 5 mM (for example, 40 mM was used in Ref. 49). With regard to this contradictory effect of NAM, it is noteworthy that 5 mM NAM inhibited SIRT1-mediated PGC-1␣ deacetylation in 293T cells, but even at 50 mM it was unable to increase PGC-1␣ acetylation when the SIRT1 protein level was increased by the adenoviral transduction of the gene (47).…”

SIRT1 modulates MAPK pathways in ischemic–reperfused cardiomyocytes

“…In contrast, sirtuin knockdown triggered cell death in isolated neonatal rat cardiomyocytes [29]. It was shown that Resv protects H9c2 cells from hypoxia-induced apoptosis by signaling via the SIRT1-FOXO1 pathway [15]. Moreover, SIRT1-induced upregulation of antioxidants and downregulation of pro-apoptotic molecules, via FOXO activation and reduction of oxidative stress, protecting transgenic mice from IR-induced cardiac injury [30].…”

“…Resv reportedly protects the heart from ischemic-reperfusion injury [14]. With regard to cardiomyoblasts, it has been suggested that Resv has direct beneficial effects against ischemia/hypoxia of cardiomyocytes, protecting these cells from apoptosis through the involvement of SIRT1 [15].…”