Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a.
Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):2909-2916. PMID: 31307244
Hypoxia-caused cardiocytes insults are closely correlated with ectopic expression of genes, which might be modulated by microRNAs (miRs). Quercetin exhibits a profound protective function against hypoxic damages in cardiomyocytes. Here, we aimed to investigate a possible underpinning. H9c2 cells were pre-administrated using quercetin before hypoxia treatment. The damages were assessed using viability, apoptosis and alteration of proteins associated with apoptosis and adenosine monophosphate-activated protein (AMPK) pathway. Transfection was conducted to enforce overexpression of miR-199a or silence of sirtuin 1 (sirt1) which were confirmed by qRT-PCR. Sirt1 protein was quantified by immunoblotting. A luciferase reporter was exploited to confirm the target relationship between miR-199a and sirt1 3'-untranslated region (3'-UTR). We found quercetin mitigated hypoxia-caused viability reduction and apoptosis with restoring apoptosis-associated protein and rescuing phosphorylation of AMPK. Quercetin flattened hypoxia-evoked overexpression of miR-199a. miR-199a abrogated the protective effects of quercetin against hypoxia-elicited damages. Quercetin elevated sirt1 which was repressed by hypoxia, while this effect was slight in miR-199a-overexpressed cells. miR-199a negatively mediated sirt1 expression through directly binding its 3'-UTR. Further, quercetin facilitated the phosphorylation of AMPK by up-regulating sirt1. Collectively, quercetin participated in repressing miR-199a which negatively modulated sirt1. Mechanically, through activating AMPK, quercetin protected cardiomyocytes cells against hypoxia-caused insults. Highlights Quercetin ameliorates hypoxia-evoked apoptosis and blockage of AMPK phosphorylation; The elevated miR-199a level is eased by quercetin, which might be a protective mechanism; Quercetin restores sirt1 level by repressing miR-199a expression; By mediating miR-199a and sirt1, AMPKphosphorylation is fortified by quercetin.