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Gallic Acid Induces Neuronal Cell Death through Activation of c‐Jun N‐Terminal Kinase and Downregulation of Bcl‐2
Author(s) -
Kang Min Kyung,
Kang Nam Joo,
Jang Young Jin,
Lee Ki Won,
Lee Hyong Joo
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04728.x
Subject(s) - gallic acid , programmed cell death , viability assay , downregulation and upregulation , apoptosis , oxidative stress , chemistry , kinase , reactive oxygen species , c jun , microbiology and biotechnology , biochemistry , biology , antioxidant , transcription factor , gene
Oxidative stress induced by reactive oxygen species (ROS) is strongly associated with the pathogenesis of various neurodegenerative disorders, including Alzheimer's disease. We investigated the possible combined effects of gallic acid and resveratrol, which are major antioxidants present in fruit, including grapes, on PC12 rat pheochromocytoma (PC12) cell death. Gallic acid did not protect against H 2 O 2 ‐induced PC12 cell death; it reduced the viability of PC12 cells in a dose‐dependent manner. Gallic acid also induced cleavage of poly (ADP‐ribose) polymerase, which is strongly related to apoptosis in neurons. Gallic acid induced the phosphorylation of c‐Jun N‐terminal protein kinase (JNK) and the downregulation of Bcl‐2 in PC12 cells. Treatment of PC12 cells with resveratrol increased their viability in a dose‐dependent manner by blocking the activation of JNK and the downregulation of Bcl‐2. Furthermore, gallic acid led to a progressive reduction in the viability of vector‐transfected PC12 cells, which was delayed in PC12 cells that overexpressed Bcl‐2. The JNK inhibitor SP600125 protected against gallic acid‐induced PC12 cell death. Collectively, these findings suggest that the combined effects of dietary phenolic phytochemicals on oxidative neuronal cell death and antioxidants differ in ROS‐mediated neuronal cell death.