• Title/Summary/Keyword: RKIP

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RKIP Downregulation Induces the HBx-Mediated Raf-1 Mitochondrial Translocation

  • Kim, Sun-Young;Park, Sung-Goo;Jung, Hye-Yun;Chi, Seung-Wook;Yu, Dae-Yeul;Lee, Sang-Chul;Bae, Kwang-Hee
    • Journal of Microbiology and Biotechnology
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    • v.21 no.5
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    • pp.525-528
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    • 2011
  • The Raf-1 kinase inhibitory protein (RKIP) can regulate multiple key signaling pathways. Specifically, RKIP binds to Raf-1 kinase and inhibits the Ras-Raf-1-MEK1/2- ERK1/2 pathway. Additionally, Raf-1 has been shown to translocate to mitochondria and thereby protect cells from stress-mediated apoptosis. Recently, HBx was found to stimulate the mitochondrial translocation of Raf-1, contributing to the anti-apoptotic effect. We found that RKIP was downregulated during HBx-mediated hepatocarcinogenesis. In this study, we show that RKIP bound to Raf-1 and consequently inhibited the translocation of Raf-1 into mitochondria. This promoted the apoptosis of cells treated with apoptotic stimulus. Thus, the downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis. The elevated Raf-1 mitochondrial translocation induced the increased anti-apoptotic effect and subsequently promoted HBx-mediated hepatocarcinogenesis.

Effects of (-)-Epigallocatechin-3-gallate on the Release of Pancreatic Enzymes and Expression of Regenerating Genes in Ethanol-injured Murine Pancreatic Primary Acinar Cells (에탄올에 의하여 유도된 마우스 췌장 선포세포의 염증성 손상에서 췌장분비 효소의 활성 및 세포 재생관련 유전자들의 발현에 미치는 EGCG의 영향)

  • Kim, Sung Ok;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.11
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    • pp.1404-1408
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    • 2013
  • (-)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has been shown to have strong antibacterial, antiviral, antioxidant, anti-inflammatory, and chemopreventive effects. However it is unknown whether EGCG can recover alcohol-associated pancreatitis. The aim of this study was to investigate the effects of EGCG on pancreatic enzyme activities and the expressions of pancreatic regenerating related markers, such as adenosine monophosphate-activated protein kinase (AMPK), raf-1 kinase inhibitor protein (RKIP), and Regenerating gene 1 (Reg1), in mice pancreatic primary acinar cells. Our results revealed that activities of ${\alpha}$-amylase and chymotrypsin were significantly increased in the cells treated with ethanol compared to the untreated control cells; however, the increased activities of both enzymes were markedly reduced by pretreatment with EGCG. Phosphorylation of AMPK and total expression of RKIP were decreased in the ethanol-treated primary acinar cells; however, these were both significantly increased in the EGCG-pretreated cells. In addition, when EGCG was treated, expression of Reg1 was markedly increased compared with that of the control or the ethanol-treated primary acinar cells, demonstrating that EGCG can modulate pancreatic regenerating related genes. Therefore, our findings suggest that EGCG may have therapeutic utility in the prevention or treatment of alcohol-associated pancreatitis.