Quercetin attenuates cardiomyocyte hypertrophy through proteasome in-hibition / 中国病理生理杂志

ABSTRACT

AIM:ToinvestigatetheprotectiveeffectofquercetinonangiotensinⅡ(AngⅡ)-inducedcardio-myocyte hypertrophy and its possible mechanism .METHODS: Cardiomyocyte hypertrophy was induced by AngⅡ ( 100 nmol/L) in primary neonatal cardiomyocytes and H 9c2 cells.The cells were treated with different concentration of querce-tin (10 μmol/L, 20 μmol/L and 40 μmol/L) for 48 h and then the cardiomyocyte surface areas were measured by immu-nofluorescence .Proteasome activity was detected by fluorescent peptide substrate .The phosphorylated levels of GSK-3α/βand Akt in H9c2 cells were determined by Western blot .RESULTS:Compared with control group , the cardiomyocyte sur-face areas were both increased in primary cultured neonatal cardiomyocytes and H 9c2 cells, while the surface areas were significantly decreased by quercetin , especially at concentration of 20 μmol/L compared with Ang Ⅱgroup (P<0.05). Compared with control group , the chymotrypsin-like, trypsin-like and caspase-like activities of proteasome were all in-creased in H9c2 cells (P<0.05).The trypsin-like and caspase-like activities of proteasome were inhibited by 20 μmol/L and 40 μmol/L quercetin , while chymotrypsin-like activity was inhibited only at 20 μmol/L of quercetin compared with AngⅡgroup (P<0.05).In addition, phosphorylated levels of GSK-3α-Ser21, GSK-3β-Ser9 and Akt-Ser473 in AngⅡgroup were all increased compared with control group , which were obviously inhibited by in 20 μmol/L and 40 μmol/L quercetin ( P<0.05 ) .CONCLUSION: Quercetin decreases cardiomyocyte hypertrophy through proteasome inhibition , which may be related to the inhibition of Akt and therefore increasing activation of GSK -3α/βin H9c2 cells.