Amylin prevents TRAIL-mediated apoptotic effects of reserpine in the rat gastric mucosa
Amylin prevents TRAIL-mediated apoptotic effects of reserpine in the rat gastric mucosa
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DOI：
10.1016/j.peptides.2009.05.005
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发表时间：
2009-08-01
期刊：
影响因子：
3
通讯作者：
Bernardini, Renato
中科院分区：
文献类型：
--
作者：
Cantarella, Giuseppina;Di Benedetto, Giulia;Bernardini, Renato
我们之前已经证明胰淀素通过细胞因子介导的机制对受损的大鼠胃粘膜具有保护作用。在这里，在体内利血平损伤的大鼠胃粘膜中测试了胰淀素对促凋亡细胞因子TNF相关凋亡诱导配体（TRAIL）的影响。成年雄性 Sprague-Dawley 大鼠腹腔内注射利血平导致胃粘膜中 TRAIL 表达增加。免疫组织化学显示TRAIL死亡受体5（DR5）由粘膜细胞组成型表达。蛋白质印迹显示，用胰淀素预处理利血平治疗的大鼠与 TRAIL 表达减弱相关。在同一样本中，我们还研究了 TRAIL 相关信号传导，并观察到在利血平治疗的大鼠中，caspase-8 和 -3 的激活与 TRAIL 表达的增加同时发生。与后者类似，用胰淀素预处理的大鼠中半胱天冬酶的激活减弱。利血平治疗与促凋亡蛋白 Bax 的表达增加相关，而抗凋亡蛋白 Bcl-2 的表达显着降低。胰淀素可以阻止利血平对这些基因的影响。利血平启动大鼠胃粘膜细胞凋亡的机制，该机制似乎至少部分是由 TRAIL 介导的。此外，TRAIL下游信号传导随着与细胞凋亡相关的基因表达的破坏而被激活。胰淀素能够防止利血平的有害作用。最后，胰岛淀粉样多肽和相关分子可被设想为胃粘膜损伤的保护剂。 (C) 2009 Elsevier Inc. 保留所有权利。
We have previously shown that amylin has a protective effect upon the damaged rat gastric mucosa via a cytokine-mediated mechanism. Here, the effects of amylin on the proapoptotic cytokine TNF-related-apoptosis-inducing-ligand (TRAIL) were tested in the rat gastric mucosa damaged by reserpine administration in vivo. Intraperitoneal administration of reserpine in adult male Sprague-Dawley rats resulted in increased TRAIL expression in the gastric mucosa. Immunohistochemistry showed that the TRAIL death-receptor 5 (DR5) was constitutively expressed by the mucosa cells. Western blot showed that pretreatment of reserpine-treated rats with amylin was associated with attenuated expression of TRAIL. In the same samples, we also investigated about TRAIL-related signaling and observed that activation of caspases-8 and -3 occurs in parallel to increased TRAIL expression in rats treated with reserpine. Similarly to the latter, activation of caspases was attenuated in rats pretreated with amylin. Treatment with reserpine was associated with increased expression of the proapoptotic protein Bax, whereas that of the antiapoptotic protein Bcl-2 was significantly decreased. Amylin prevented the effects of reserpine on these genes. Reserpine sets into motion mechanisms of apoptosis in the rat gastric mucosa, which appear mediated, at least in part, by TRAIL. In addition, TRAIL downstream signaling is activated along with subversion of gene expression related to apoptosis. Amylin was able to prevent detrimental effects of reserpine. Finally, amylin and related molecules may be envisioned as protective agent in gastric mucosa damage. (C) 2009 Elsevier Inc. All rights reserved.