H-89 potentiates adipogenesis in 3T3-L1 cells by activating insulin signaling independently of protein kinase A
- 作者：Yoshiro Kato ; Nobuaki Ozaki ; Tsutomu Yamada ; Yoshitaka Miura ; Yutaka Oiso
- 关键词：3T3-L1 cells ; Adipogenesis ; H-89 ; Protein kinase A ; Rho kinase ; Phosphoinositide 3-kinase ; Akt ; Ras ; Extracellular signal-regulated kinase 1/2
- 刊名：Life Sciences
- 出版年：2007
- 期刊代码：62_00243205
- 类别：imm
- 出版时间：9 January 2007
- 卷：80
- 期：5
- 页码：476-483
- 文件大小：441 K
摘要
Among four kinds of protein kinase A (PKA) inhibitors tested, H-89 exhibited a unique action to remarkably enhance adipocyte differentiation of 3T3-L1 cells, whereas the other three PKA inhibitors, PKA inhibitor Fragment 14–22 (PKI), Rp-cAMP, and KT 5720, did not enhance adipocyte differentiation. H-85, which is an inactive form of H-89, exhibited a similar enhancing effect on adipocyte differentiation. H-89 also potentiated the phosphorylation of Akt and extracellular signal-regulated kinase (ERK) 1/2 in 3T3-L1 cells, which function as downstream signaling of insulin. Phosphoinositide 3-kinase (PI3K) inhibitor wortmannin and mitogen-activated protein kinase kinase (MEK) inhibitor PD 98059 suppressed both the H-89-induced promotion of adipocyte differentiation and the H-89-induced potentiation of phosphorylation of Akt and ERK1/2. Rho kinase inhibitor Y-27632 also promoted the phosphorylation of both Akt and ERK1/2 and enhanced adipocyte differentiation, although its effect was somewhat less than that of H-89. Even when cells were treated with a mixture of Y-27632 and H-89, the additive enhancing effects on both the insulin signaling and adipocyte differentiation were not detected. Therefore, it is suggested that the major possible mechanism whereby H-89 potentiates adipocyte differentiation of 3T3-L1 cells is activation of insulin signaling that is elicited mostly by inhibiting Rho/Rho kinase pathway.