Gene expression profiling identifies the novel role of immunoproteasome in XXXX -induced @entity1370 .

@entity632 @entity19 @entity3105 @entity1370
The most well-known cause of chemotherapy-induced @entity1370 is @entity632 ( @entity3105 ). The ubiquitin-proteasome system (UPS) is the main cellular machinery for protein degradation in eukaryotic cells. However, the expression pattern of the UPS in @entity3105 -induced @entity1370 remains unclear. C57BL/6 @entity19 were intraperitoneally injected with a single dose of @entity3105 (15mg/kg). After 1, 3 and 5 days, cardiac function and apoptosis were detected with echocardiography and TUNEL assay. Microarray assay and qPCR analysis were also performed at day 5. We found that @entity3105 caused a significant decrease in cardiac function at day 5 and increase in cardiomyocyte apoptosis at days 3 and 5. Microarray data revealed that totally 1185 genes were significantly regulated in @entity3105 -treated heart, and genes involved in apoptosis and the UPS were mostly altered. Among them, the expression of 3 immunoproteasome catalytic subunits (b1i, b2i and b5i) was markedly down-regulated. Moreover, @entity3105 significantly decreased proteasome activities and enhanced polyubiquitinated proteins in the heart. Importantly, overexpression of immunoproteasome catalytic subunits (b1i, b2i or b5i) significantly attenuated @entity3105 -induced cardiomyocyte apoptosis and other UPS gene expression while knockdown of them significantly increased @entity3105 -induced cardiomyocyte apoptosis. These effects were partially associated with increased degradation of multiple pro-apoptotic proteins. In conclusion, our studies suggest that immunoproteasome plays an important role in @entity3105 -induced cardiomyocyte apoptosis, and may be a novel therapeutic target for prevention of @entity3105 -induced @entity1370 .
