The role of atenolol in the modulation of the expression of genes encoding pro- (caspase-1) and anti- (Bcl2L1) apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats

Abstract

Purpose: To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR). Methods: Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68). Conclusions: Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.

Corticosterone induces obesity partly via promoting intestinal cell proliferation and survival

“…The heatmap indicated that of the 33 genes, 11 genes were up-regulated and 22 genes were down-regulated in CORT-treated group. We identified 5 genes ( Glul , Wee1 , Xiap , Casp1 and Casp7 ) ( Figure 3F ), which were reported to mediate apoptosis resistance and cell proliferation ( 13 – 22 ). This result suggested that CORT-induced increased intestinal length might be due to activation of signaling pathways associated with cell proliferation and apoptosis resistance.…”

“…Caspase family are essential for the initiation and execution of apoptosis ( 20 ). In murine model of intestinal ischemia-reperfusion (ICR) injury, the expression levels of Casp1 and Casp7 were significantly increased, while reducing Casp1 and Casp7 suppressed ICR-induced intestinal epithelial cell apoptosis ( 21 , 22 ). Xiap showed its apoptosis resistance effect by repressing Casp7 using both an active site-directed mechanism and non-competitive mechanism ( 19 ).…”