Antistress effect of red ginseng in brain cells is mediated by TACE repression via PADI4

作者：Kim Eun Hye; Kim In Hye; Ha Jung Ah; Choi Kwang Tae; Pyo Suhkneung; Rhee Dong Kwon^*

来源：Journal of Ginseng Research, 2013, 37(3): 315-323.

DOI：10.5142/jgr.2013.37.315

• Panax ginseng
• Oxidative stress
• Peptidyl arginine deiminase type IV
• Tumor necrosis factor-alpha converting enzyme
• Nuclear factor-kappa B

Ginseng is known to have antistress effects. Previously, red ginseng (RG) was shown to repress stress-induced peptidyl arginine deiminase type IV (PADI4) via estrogen receptor beta (ER beta) in the brain, thus inhibiting brain cell apoptosis. Moreover, tumor necrosis factor (TNF)-alpha plays a critical role in immobilization (MO) stress. However, the signaling pathway of RG-mediated repressesion of inflammation is not completely understood. In this study, we determined how RG modulated gene expression in stressed brain cells. Since secretion of TNF-alpha is modulated via TNF-alpha converting enzyme (TACE) and nuclear factor (NF)-kappa B, we examined the inflammatory pathway in stressed brain cells. Immunohistochemistry revealed that TACE was induced by IMO stress, but RG repressed TACE induction. Moreover, PADI4 siRNA repressed TACE expression compared to the mock transfected control suggesting that PADI4 was required for TACE expression. A reporter assay also revealed that H2O2 oxidative stress induced NF-kappa B in neuroblastoma SK-N-SH cells, however, RG pretreatment repressed NF-kappa B induction. These findings were supported by significant induction of nitric oxide and reactive oxygen species (ROS) by oxidative stress, which could be repressed by RG administration. Taken together, RG appeared to repress stress-induced PADI4 via TACE and NF-kappa B in brain cells thus preventing production of ROS and subsequently protecting brain cells from apoptosis.

• 出版日期2013-7