Takai Shinji, Matsushima-Nishiwaki Rie, Tokuda Haruhiko, Yasuda Eisuke, Toyoda Hidenori, Kaneoka Yuji, Yamaguchi Akihiro, Kumada Takashi, Kozawa Osamu
Department of Pharmacology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Japan.
Life Sci. 2007 Jul 26;81(7):585-91. doi: 10.1016/j.lfs.2007.06.018. Epub 2007 Jul 3.
We have recently reported that attenuated phosphorylation of heat shock protein (HSP) 27 correlates with tumor progression in patients with hepatocellular carcinoma (HCC). In the present study, we investigated what kind of kinase regulates phosphorylation of HSP27 in human HCC-derived HuH7 cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleoyl-2-acetylglycerol, direct activators of protein kinase C (PKC), markedly strengthened the phosphorylation of HSP27. Bisindorylmaleimide I, an inhibitor of PKC, suppressed the TPA-induced levels of HSP27 phosphorylation in addition to its basal levels. Knock down of PKCdelta suppressed HSP27 phosphorylation, as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. SB203580, an inhibitor of p38 MAPK, suppressed the TPA-induced HSP27 phosphorylation. Our results strongly suggest that activation of PKCdelta regulates the phosphorylation of HSP27 via p38 MAPK in human HCC.
我们最近报道，热休克蛋白（HSP）27磷酸化减弱与肝细胞癌（HCC）患者的肿瘤进展相关。在本研究中，我们调查了在人肝癌衍生的HuH7细胞中，何种激酶调节HSP27的磷酸化。12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）和1 - 油酰 - 2 - 乙酰甘油，蛋白激酶C（PKC）的直接激活剂，显著增强了HSP27的磷酸化。双吲哚马来酰亚胺I，一种PKC抑制剂，除了抑制其基础水平外，还抑制了TPA诱导的HSP27磷酸化水平。敲低PKCδ可抑制HSP27磷酸化以及p38丝裂原活化蛋白激酶（MAPK）磷酸化。p38 MAPK抑制剂SB203580抑制了TPA诱导的HSP27磷酸化。我们的结果强烈表明，在人类肝癌中，PKCδ的激活通过p38 MAPK调节HSP27的磷酸化。
