Gallic Acid Induces Apoptosis of Lung Fibroblasts via a Reactive Oxygen Species-Dependent Ataxia Telangiectasia Mutated-p53 Activation Pathway

doi:10.1021/jf9043265

南華大學機構典藏系統 > 科技學院 > 自然生物科技學系(自然療癒碩士班) > 期刊論文 > Item 987654321/29391

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题名:	Gallic Acid Induces Apoptosis of Lung Fibroblasts via a Reactive Oxygen Species-Dependent Ataxia Telangiectasia Mutated-p53 Activation Pathway
作者:	陳秋媛;Chen, Chiu-Yuan
貢獻者:	自然生物科技學系
关键词:	Idiopathic pulmonary fibrosis;gallic acid;apoptosis;reactive oxygen species;p53;ataxia telangiectasia mutated
日期:	2010
上传时间:	2022-12-19 16:31:42 (UTC+8)
摘要:	Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder characterized by the activation of fibroblasts and the overproduction of extracellular matrix. Fibroblast resistance to apoptosis leads to increased fibrosis. Targeting fibroblasts with apoptotic agents represents a major therapeutic intervention for debilitating IPF. Gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. However, the effects of gallic acid on lung fibroblasts have not been investigated. The aim of the present study is to determine the effects of gallic acid on primary cultured mouse fibroblasts. Our results showed that gallic acid induces the apoptotic death of fibroblasts via both intrinsic and extrinsic apoptotic pathways by the elevation of PUMA, Fas, and FasL protein levels. Moreover, intracellular reactive oxygen species (ROS) generation and 8-hydroxy-2′-deoxyguanosine production were observed in gallic acid-stimulated fibroblasts. Mechanistic studies showed that gallic acid induces early phosphorylation of p53Ser18 and histone 2AXSer139 (H2AX) via ataxia telangiectasia mutated (ATM) activation in response to ROS-provoked DNA damage. When mouse lung fibroblasts were treated with caffeine, an ATM kinase inhibitor, the levels of p53, phosphorylated p53Ser18, and cell death induced by gallic acid were significantly attenuated. Additionally, pretreatment with antioxidants drastically inhibited the gallic acid-induced 8-hydroxy-2′-deoxyguanosine (8-OH-dG) formation and phosphorylation of p53Ser18 and ATMSer1981, as well as apoptosis. Our results provide the first evidence of the activation of ROS-dependent ATM/p53 signaling as a critical mechanism of gallic acid-induced cell death in primary cultured mouse lung fibroblasts.
關聯:	J. Agric. Food Chem. vol. 58, no. 5 pp.2943-2951
显示于类别:	[自然生物科技學系(自然療癒碩士班)] 期刊論文

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