Surova Olga V, Nagibin Vasyl S, Tumanovskaya Lesya V, Dosenko Victor E, Moibenko Alexey A
Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kiev, Ukraine.
Exp Clin Cardiol. 2009 Summer;14(2):e57-61.
Recent data suggest that low concentrations of proteasome inhibitors (PIs) are cytoprotective in models of ischemia-reperfusion injury, but the underlying mechanisms of this effect still remain unclear.
To investigate the effect of 100 nM of clasto-lactacystin beta-lactone on cell death and gene expression in neonatal rat cardiomyocytes exposed to anoxia-reoxygenation.
Fluorescent microscopy and real-time polymerase chain reaction were used to detect different types of cell death and gene expression, respectively, in neonatal rat cardiomyocyte cultures exposed to anoxia-reoxygenation.
It was shown that a low dose of clasto-lactacystin beta-lactone protected the cells against anoxia-reoxygenation injury by a reduction in the number of necrotic and apoptotic cells. The number of autophagic cells was greatly increased by proteasomal inhibition. The PI increased the heat shock protein 70 messenger RNA expression twofold and slightly reduced the expression of heat shock protein 90 gene. The expression of the FK506 binding protein 12-rapamycin associated protein gene was increased 1.57-fold on PI application. The B-cell lymphoma 2 gene expression was unaffected by the use of clasto-lactacystin beta-lactone in low dose.
Although PIs are injurious, they may be cardioprotective in low doses; ie, they do not result in cell death. Moreover, PIs initiate the protective mechanisms that prevent cell damage by changing the expression of several genes.
近期数据表明，低浓度蛋白酶体抑制剂（PIs）在缺血再灌注损伤模型中具有细胞保护作用，但其作用的潜在机制仍不清楚。
研究100 nM的氯抑素β-内酯对新生大鼠心肌细胞缺氧复氧后细胞死亡和基因表达的影响。
分别采用荧光显微镜和实时聚合酶链反应检测新生大鼠心肌细胞培养物在缺氧复氧后不同类型的细胞死亡和基因表达。
结果表明，低剂量的氯抑素β-内酯通过减少坏死和凋亡细胞数量来保护细胞免受缺氧复氧损伤。蛋白酶体抑制使自噬细胞数量大幅增加。PI使热休克蛋白70信使核糖核酸表达增加两倍，并略微降低热休克蛋白90基因的表达。应用PI后，FK506结合蛋白12-雷帕霉素相关蛋白基因的表达增加1.57倍。低剂量使用氯抑素β-内酯对B细胞淋巴瘤2基因表达无影响。
尽管PIs具有损伤作用，但低剂量时可能具有心脏保护作用；即它们不会导致细胞死亡。此外，PIs通过改变多个基因的表达启动保护机制，防止细胞损伤。
