Endoplasmic Reticulum Stress-Mediated Autophagy/Apoptosis Induced by Capsaicin (8-Methyl-N-vanillyl-6-nonenamide) and Dihydrocapsaicin is Regulated by the Extent of c-Jun NH2-Terminal Kinase/Extracellular Signal-Regulated Kinase Activation in WI38 Lung Epithelial Fibroblast Cells
Endoplasmic Reticulum Stress-Mediated Autophagy/Apoptosis Induced by Capsaicin (8-Methyl-N-vanillyl-6-nonenamide) and Dihydrocapsaicin is Regulated by the Extent of c-Jun NH2-Terminal Kinase/Extracellular Signal-Regulated Kinase Activation in WI38 Lung Epithelial Fibroblast Cells
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DOI：
10.1124/jpet.108.144113
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发表时间：
2009-04-01
影响因子：
3.5
通讯作者：
Lim, Sung-Chul
中科院分区：
文献类型：
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作者：
Oh, Seon-Hee;Lim, Sung-Chul
内质网应激导致细胞的生存或死亡，这取决于细胞的类型和刺激。辣椒素（8-甲基-n -vanillyl-6-nonenamide）及其类似物二氢辣椒素（dihydrocapsaicin， DHC）在WI38肺上皮成纤维细胞中诱导caspase-3独立/依赖信号通路。在这里，我们描述了这两种化学物质诱导的分子机制。暴露于辣椒素或DHC可诱导p53、p21和G(0)/G(1)阻滞。DHC通过内质网和线粒体的扩张诱导大量细胞空泡化。经典内质网胁迫诱导剂引起未折叠蛋白反应（UPR）和微管相关蛋白1轻链-3 (LC3) II的上调。DHC通过重链结合蛋白、IRE1、Chop、真核起始因子2 α和caspase-4的作用诱导内质网应激，辣椒素处理在一定程度上诱导内质网应激。DHC诱导的自噬被3-甲基腺嘌呤（3MA）阻断，并被巴菲霉素A1积累。3MA阻断dhc诱导的自噬增强了凋亡细胞的死亡，而3MA完全抑制了凋亡细胞的死亡
Endoplasmic reticulum (ER) stress causes cell survival or death, which is dependent on the type of cell and stimulus. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) and its analog, dihydrocapsaicin (DHC), induced caspase-3-independent/-dependent signaling pathways in WI38 lung epithelial fibroblast cells. Here, we describe the molecular mechanisms induced by both chemicals. Exposure to capsaicin or DHC caused induction of p53, p21, and G(0)/G(1) arrest. DHC induced massive cellular vacuolization by dilation of the ER and mitochondria. Classic ER stress inducers elicited the unfolded protein response (UPR) and up- regulation of microtubuleassociated protein 1 light chain-3 (LC3) II. DHC induced ER stress by the action of heavy chain-binding protein, IRE1, Chop, eukaryotic initiation factor 2 alpha, and caspase-4 and, to a lesser level, by capsaicin treatment. DHC treatment induced autophagy that was blocked by 3-methyladenine (3MA) and accumulated by bafilomycin A1. Blocking of DHC-induced autophagy by 3MA enhanced apoptotic cell death that was completely inhibited by