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Hepatocyte growth factor protects gastric epithelial cells against ceramide-induced apoptosis through induction of cyclooxygenase-2

机译:肝细胞生长因子通过诱导环氧合酶2保护胃上皮细胞免受神经酰胺诱导的凋亡

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摘要

Forced overexpression of cyclooxygenase-2 (COX-2) in intestinal cells has been shown to be associated with resistance to apoptosis. However, the role of physiologically-induced COX-2 in the regulation of apoptosis remains unclear. In the present study, we examined whether hepatocyte growth factor (HGF)-induced COX-2 affects ceramide-induced apoptosis in RGM-1 gastric epithelial cells. An externally applied cell permeable ceramide analogue, C-2-ceramide, caused RGM-1 cell death in a dose-dependent manner, whereas an inactive ceramide analogue, C-2-dihydroceramide, did not. TdT-mediated dUTP nick end labeling (TUNEL) assay showed that the C-2-cersunide-induced cell death was apoptosis. Application of HGF rapidly induced the expression of COX-2, and HGF prevented the apoptotic cell death induced by C-2-ceramide. However, the anti-apoptotic action of HGF was antagonized by coapplication of NS-398, a selective inhibitor of COX-2. Thus, these results indicate that COX-2 is involved in the survival signaling from HGF in gastric epithelial cells, and suggest a role for physiologically-induced COX-2 in the protection of the cells from apoptosis. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 35]
机译:肠道细胞中环氧合酶2(COX-2)的强制过度表达与抗凋亡相关。然而,尚不清楚生理诱导的COX-2在细胞凋亡的调节中的作用。在本研究中,我们检查了肝细胞生长因子(HGF)诱导的COX-2是否影响神经酰胺诱导的RGM-1胃上皮细胞凋亡。外用的细胞可渗透的神经酰胺类似物C-2-神经酰胺以剂量依赖性方式引起RGM-1细胞死亡,而无活性的神经酰胺类似物C-2-二氢神经酰胺则没有。 TdT介导的dUTP缺口末端标记(TUNEL)分析表明,C-2-cersunide诱导的细胞死亡是凋亡。 HGF的应用迅速诱导了COX-2的表达,HGF阻止了C-2-神经酰胺诱导的凋亡细胞死亡。然而,通过共同应用NS-398(一种COX-2的选择性抑制剂)来拮抗HGF的抗凋亡作用。因此,这些结果表明COX-2参与了胃上皮细胞中HGF的存活信号,并暗示了生理诱导的COX-2在保护细胞免于凋亡中的作用。 (C)2000 Elsevier Science Inc.保留所有权利。 [参考:35]

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