Insulin-like growth factor-1 (IGF-1) inhibits the basolateral Cl channels in the thick ascending limb of the rat kidney.
Insulin-like growth factor-1 (IGF-1) inhibits the basolateral Cl channels in the thick ascending limb of the rat kidney.
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DOI：
10.1016/j.bbamcr.2012.04.015
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发表时间：
2012-07
影响因子：
5.1
通讯作者：
Gu, Ruimin
中科院分区：
文献类型：
--
作者：
Wang, Lijun;Li, Wennan;Kong, Shumin;Wu, Peng;Zhang, Chengbiao;Gu, Li;Wang, Mingxiao;Wang, WenHui;Gu, Ruimin
本研究的目的是验证胰岛素样生长因子-1（IGF-1）在粗升支（TAL）基底外侧氯通道调节中发挥作用的假设。膜片钳实验表明，应用IGF-I或胰岛素抑制基底外侧10-pS Cl通道。然而，抑制Cl通道50%（K1/2）所需的胰岛素浓度比IGF-1高10倍。IGF-I对10-pS Cl通道的抑制作用可通过抑制蛋白酪氨酸激酶或阻断磷脂酰肌醇3-激酶（PI 3 K）而被阻断。与此相反，磷脂酶C（PLC）的抑制未能取消IGF-1的抑制作用对Cl通道的TAL。Western blot分析表明，IGF-1显着增加磷脂依赖性激酶（PDK）的丝氨酸残基241（Ser 241）和AKT的Ser 473在分离的髓质TAL的磷酸化。此外，用LY 294002抑制PI 3 K可消除IGF-1对PDK和AKT磷酸化的影响。雷帕霉素完全消除了IGF-1对TAL中10-pS Cl通道的作用，这进一步表明IGF-1对10-pS Cl通道的作用是由PDK-AKT-mTOR途径的刺激诱导的。我们得出结论，IGF-1通过激活PI 3 K-AKT-mTOR通路抑制基底外侧Cl通道。IGF-1对Cl-通道的抑制作用可能通过IGF-1减轻缺血性肾损伤而发挥作用。
The aim of the present study is to test the hypothesis that insulin-like-growth factor-1 (IGF-1) plays a role in the regulation of basolateral Cl channels in the thick ascending limb (TAL). The patch-clamp experiments demonstrated that application of IGF-I or insulin inhibited the basolateral 10-pS Cl channels. However, the concentration of insulin required for the inhibition of the Cl channels by 50% (K1/2) was ten times higher than those of IGF-1. The inhibitory effect of IGF-I on the 10-pS Cl channels was blocked by suppressing protein tyrosine kinase or by blocking phosphoinositide 3-kinase (PI3K). In contrast, inhibition of phospholipase C (PLC) failed to abolish the inhibitory effect of IGF-1 on the Cl channels in the TAL. Western blot analysis demonstrated that IGF-1 significantly increased the phosphorylation of phospholipid-dependent kinase (PDK) at serine residue 241 (Ser241) and AKT at Ser473 in the isolated medullary TAL. Moreover, inhibition of PI3K with LY294002 abolished the effect of IGF-1 on the phosphorylation of PDK and AKT. The notion that the effect of IGF-1 on the 10-pS Cl channels was induced by stimulation of PDK-AKT-mTOR pathway was further suggested by the finding that rapamycin completely abolished the effect of IGF-1 on the 10-pS Cl channels in the TAL. We conclude that IGF-1 inhibits the basolateral Cl channels by activating PI3K-AKT-mTOR pathways. The inhibitory effect of IGF-1 on the Cl channels may play a role in ameliorating the ischemia-induced renal injury through IGF-1 administration.
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影响因子：
4.8
作者：
Harwood, Franklin C.;Shu, Lili;Houghton, Peter J.
通讯作者：
Houghton, Peter J.
DOI：
10.1073/pnas.86.8.2868
发表时间：
1989-04-01
影响因子：
11.1
作者：
GULER, HP;SCHMID, C;FROESCH, ER
通讯作者：
FROESCH, ER
影响因子：
4.8
作者：
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通讯作者：
Lin, Richard Z.
影响因子：
4.8
作者：
Kamenicky, Peter;Viengchareun, Say;Lombes, Marc
通讯作者：
Lombes, Marc
影响因子：
5.5
作者：
GUINAMARD, R;CHRAIBI, A;TEULON, J
通讯作者：
TEULON, J