title: Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH2-Terminal Kinase-Dependent Apoptosis in Lung Fibroblasts.
abstract: Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts.
authors.affiliation: Graduate Institute of Natural Healing Sciences, Nanhua University, No. 55, Section 1, Nanhua Road, Zhongkeng, Dalin Township, Chiayi County 622, Taiwan.
authors.forename: Chiu-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Kun-Chieh
authors.initials: KC
authors.lastname: Chen
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Liu
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu