MG132, a proteasome inhibitor, attenuates pressure-overload-induced cardiac hypertrophy in rats by modulation of mitogen-activated protein kinase signals.
Proteasome inhibitors are involved in cell cycle control, growth and inflammatory signaling, and transcriptional regulation of mitotic cells. A recent study has suggested that specific proteasome inhibitor MG132 may suppress cardiomyocyte hypertrophy in vitro. However, the underlying molecular mechanisms are not clear. In this study, we investigated the effects of long-term MG132 treatment on cardiac hypertrophy and the related molecular mechanisms in vivo. MG132 (0.1 mg/kg/day) was intraperitoneally injected to rats with abdominal aortic banding (AAB) for 8 weeks. Results showed that treatment with MG132 significantly attenuated left ventricular (LV) myocyte area, LV weight/body weight, and lung weight/body weight ratios, decreased LV diastolic diameter and wall thickness, and increased fractional shortening in AAB rats. AAB induced the phosphorylation of ERK1/2, JNK1, and p38 in cardiac myocytes. The elevated phosphorylation levels of ERK1/2 and JNK1 in AAB rats were significantly reversed by MG132 treatment. In conclusion, our results suggested that long-term treatment with MG132 attenuates pressureoverload-induced cardiac hypertrophy and improves cardiac function in AAB rats through regulation of ERK1/2 and JNK1 signaling pathways.
Chen
Baolin
B
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Ma
Yuedong
Y
Meng
Rongsen
R
Xiong
Zhaojun
Z
Zhang
Chengxi
C
Chen
Guangqin
G
Zhang
Aixia
A
Dong
Yugang
Y
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D006332:Cardiomegaly / Q000473:pathology*; D004452:Echocardiography / Q000379:methods; D006352:Heart Ventricles / Q000473:pathology; D007976:Leupeptins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008297:Male; D010766:Phosphorylation; D011312:Pressure; D011480:Protease Inhibitors / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D007976:Leupeptins; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde