Kozawa O, Niwa M, Matsuno H, Ishisaki A, Kato K, Uematsu T
Department of Pharmacology, Gifu University School of Medicine, Japan.
Arch Biochem Biophys. 2001 Apr 15;388(2):237-42. doi: 10.1006/abbi.2000.2290.
In a previous study we showed that basic fibroblast growth factor (bFGF) stimulates activation of protein kinase C through phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether bFGF stimulates the induction of heat shock protein (HSP) 27, a low-molecular-weight HSP, and HSP70, a high-molecular-weight HSP, in MC3T3-E1 cells and the mechanism behind the induction. bFGF increased the level of HSP27 while having little effect on HSP70 level. bFGF stimulated the accumulation of HSP27 dose-dependently in the range between 1 and 30 ng/ml. bFGF induced an increase in the level of the mRNA for HSP27. The bFGF-stimulated accumulation of HSP27 was reduced by inhibitors of protein kinase C. The bFGF-induced HSP27 accumulation was reduced in protein kinase C-downregulated MC3T3-E1 cells. U-73122, an inhibitor of phospholipase C, and propranolol, a phosphatidic acid phosphohydrolase inhibitor, suppressed the bFGF-stimulated HSP27 accumulation. These results strongly suggest that bFGF stimulates HSP27 induction through protein kinase C activation in osteoblasts.
在先前的一项研究中，我们发现碱性成纤维细胞生长因子（bFGF）通过磷脂酶C介导的磷酸肌醇水解以及磷脂酶D介导的磷脂酰胆碱水解，刺激成骨样MC3T3-E1细胞中蛋白激酶C的激活。在本研究中，我们调查了bFGF是否能刺激MC3T3-E1细胞中低分子量热休克蛋白（HSP）27和高分子量热休克蛋白HSP70的诱导表达以及诱导背后的机制。bFGF增加了HSP27的水平，而对HSP70水平影响甚微。在1至30 ng/ml的范围内，bFGF剂量依赖性地刺激了HSP27的积累。bFGF诱导了HSP27 mRNA水平的增加。蛋白激酶C抑制剂降低了bFGF刺激的HSP27积累。在蛋白激酶C下调的MC3T3-E1细胞中，bFGF诱导的HSP27积累减少。磷脂酶C抑制剂U-73122和磷脂酸磷酸水解酶抑制剂普萘洛尔抑制了bFGF刺激的HSP27积累。这些结果强烈表明，bFGF通过激活成骨细胞中的蛋白激酶C来刺激HSP27的诱导表达。
