Xia X, Serrero G
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, USA.
J Cell Physiol. 1999 Jan;178(1):9-16. doi: 10.1002/(SICI)1097-4652(199901)178:1<9::AID-JCP2>3.0.CO;2-#.
Phosphatidylinositol (PI) 3-kinase plays an important role in various cellular signaling mechanisms in several cell systems. The role of PI 3-kinase in adipose differentiation was investigated. For this purpose, we examined the effect of specific inhibitors of PI 3-kinase on the differentiation of two adipogenic cell lines, 1246 and 3T3-L1. The results show that two structurally different inhibitors of PI 3-kinase, i.e., LY294002 and wortmannin, blocked adipose differentiation in a time and dose-dependent fashion. The results from time- course studies indicated that PI 3-kinase activity is most important in the early phase (day 4 to day 6) of the differentiation program. The effect of PI 3-kinase inhibitor on the expression of the peroxisome proliferator-activated receptor (PPAR) gamma, a master regulator in adipogenesis induced during the differentiation process, was also examined. LY294002 significantly inhibited the induction of PPARgamma mRNA expression. During the initiation phase of adipogenesis (day 4 to day 6), the expression of PPARgamma was induced and LY294002 blocked the increase of expression of PPARgamma mRNA. The inhibition of expression of PPARgamma may provide a molecular mechanism for the action of PI 3-kinase inhibitors on adipose differentiation.
磷脂酰肌醇-3激酶（PI 3-激酶）在多种细胞系统的不同细胞信号传导机制中发挥着重要作用。研究了PI 3-激酶在脂肪分化中的作用。为此，我们检测了PI 3-激酶特异性抑制剂对两种脂肪生成细胞系1246和3T3-L1分化的影响。结果表明，两种结构不同的PI 3-激酶抑制剂，即LY294002和渥曼青霉素，以时间和剂量依赖的方式阻断脂肪分化。时间进程研究结果表明，PI 3-激酶活性在分化程序的早期阶段（第4天至第6天）最为重要。还检测了PI 3-激酶抑制剂对过氧化物酶体增殖物激活受体（PPAR）γ表达的影响，PPARγ是分化过程中诱导脂肪生成的主要调节因子。LY294002显著抑制PPARγ mRNA表达的诱导。在脂肪生成的起始阶段（第4天至第6天），PPARγ的表达被诱导，LY294002阻断了PPARγ mRNA表达的增加。PPARγ表达的抑制可能为PI 3-激酶抑制剂对脂肪分化的作用提供一种分子机制。
