The endoplasmic reticulum stress-mediated apoptosis signal pathway is involved in sepsis-induced abnormal lymphocyte apoptosis
The endoplasmic reticulum stress-mediated apoptosis signal pathway is involved in sepsis-induced abnormal lymphocyte apoptosis
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DOI：
10.1159/000135631
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发表时间：
2008-01-01
影响因子：
1.6
通讯作者：
Xue, C.
中科院分区：
文献类型：
--
作者：
Ma, T.;Han, L.;Xue, C.
背景/目的：脓毒症中淋巴细胞异常凋亡的机制仅部分明确。本研究旨在探讨内质网（ER）是否与脓毒症中淋巴细胞的广泛凋亡有关。方法：C57BL/6小鼠随机分为盲肠结扎穿刺（CLP）组和假手术组。采用TUNEL法和流式细胞术检测细胞凋亡。 RT-PCR和Western blot检测葡萄糖调节蛋白78（GRP78）和C/EBP同源蛋白（CHOP）的表达。通过 RT-PCR 检测 X 盒结合蛋白 1 (XBP1) mRNA 的剪接。结果：CLP组中观察到高度的淋巴细胞凋亡。在脓毒症小鼠的脾细胞中观察到 GRP78 的显着诱导和剪接的 XBP1 mRNA 的积累，表明未折叠蛋白反应的激活。此外，CLP 组中 CHOP 及其 mRNA 均显着上调，表明 ER 应激反应转变为促凋亡反应。结论：这些数据表明淋巴细胞中未折叠蛋白反应的激活，并且 ER 应激可能导致脓毒症期间淋巴细胞异常凋亡。因此，ER应激介导的细胞凋亡途径可能成为临床预防和治疗脓毒症诱导的淋巴细胞凋亡的新靶点。版权所有 (C) 2008 S. Karger AG，巴塞尔。
Background/Aim: The mechanisms of abnormal lymphocyte apoptosis in sepsis are only partially defined. The present study was designed to investigate whether the endoplasmic reticulum (ER) is implicated in the extensive apoptosis of lymphocytes in sepsis. Methods: C57BL/6 mice were randomized into cecal ligation and puncture (CLP) and sham operation groups. Apoptosis was detected by the TUNEL method and flow cytometry. The expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) was detected by RT-PCR and Western blot. The splicing of X box-binding protein-1 (XBP1) mRNA was detected by RT-PCR. Results: A high degree of lymphocyte apoptosis was observed in the CLP group. Marked induction of GRP78 and accumulation of spliced XBP1 mRNA were observed in the splenocytes from septic mice, indicating activation of unfolded protein responses. Furthermore, both CHOP and its mRNA were markedly upregulated in the CLP group, suggesting that the ER stress response switched to a proapoptotic response. Conclusion: These data demonstrate activation of the unfolded protein response in lymphocytes and that ER stress may contribute to abnormal lymphocyte apoptosis during sepsis. Accordingly, the ER stress-mediated apoptosis pathway may be a novel target in clinical prevention and therapy of sepsis-induced lymphocyte apoptosis. Copyright (C) 2008 S. Karger AG, Basel.