Insulin/IGF-I rescues immortalized brown adipocytes from apoptosis down-regulating Bcl-xS expression, in a PI 3-kinase- and map kinase-dependent manner
Insulin/IGF-I rescues immortalized brown adipocytes from apoptosis down-regulating Bcl-xS expression, in a PI 3-kinase- and map kinase-dependent manner
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DOI：
10.1006/excr.1998.4168
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发表时间：
1998-09-15
影响因子：
3.7
通讯作者：
Lorenzo, M
中科院分区：
文献类型：
--
作者：
Navarro, P;Valverde, AM;Lorenzo, M
通过DNA阶梯或次二倍体细胞百分比的增加检测到，血清剥夺永生化棕色脂肪细胞系导致细胞周期的G0/G1期生长停滞和凋亡。此外，凋亡与促凋亡蛋白Bcl-xS的表达显著增加同时发生，而Bcl-xL的表达几乎无法检测到。胰岛素/胰岛素样生长因子（IGF-I）挽救了血清缺失的棕色脂肪细胞免于凋亡，减少了次二倍体细胞的数量，增加了在细胞周期的S期和G2/M期进行细胞周期进展的细胞数量。胰岛素下调Bcl-xS的表达，但不诱导Bcl-xL的表达。磷脂酰肌醇（PI） 3-激酶和丝裂原活化蛋白激酶（MAPK）途径都是胰岛素/IGF-I完全存活效应所必需的，因为使用特异性PI 3-激酶活性抑制剂（wortmannin或LY294002，其剂量抑制胰岛素诱导的PI 3-激酶活性）或MAPK激酶活性抑制剂（PD098059，其剂量抑制胰岛素诱导的MAPK磷酸化）分别完全阻断胰岛素/IGF-I诱导的抗凋亡作用。综上所述，胰岛素对永生化棕色脂肪细胞的存活影响与抑制Bcl-xS含量而不改变Bcl-xL有关，以PI 3-激酶和MAP激酶依赖的方式。(C) 1998学术出版社。
Serum deprivation of immortalized brown adipocyte cell line resulted in growth arrest in G0/G1 phases of the cell cycle and apoptosis, as detected either by DNA laddering or by increase in the percentage of hypodiploid cells. Furthermore, apoptosis is concurrent with a dramatic increase in the expression of the proapoptotic protein Bcl-xS, the expression of Bcl-xL remaining almost undetectable. Insulin/insulin-like growth factor (IGF-I) rescued serum-deprived brown adipocytes from apoptosis, decreasing the number of hypodiploid cells and increasing the number of cells undergoing cell cycle progression throughout S and G2/M phases of the cell cycle. Moreover, insulin down-regulated Bcl-xS expression without inducing the expression of Bcl-xL. Both phosphatidylinositol (PI) 3-kinase and mitogen-activated protein kinase (MAPK) pathways are necessary for insulin/IGF-I full survival effect, since the use of specific inhibitors of PI 3-kinase activity (wortmannin or LY294002, at the dose that inhibits PI 3-kinase activity induced by insulin) or MAPK kinase activity inhibitor (PD098059, at the dose that inhibits insulin-induced phosphorylation of MAPK) totally blocked the antiapoptotic effect induced by insulin/IGF-I, respectively. In conclusion, insulin survival effect on immortalized brown adipocytes is associated with inhibition of the Bcl-xS content without changing Bcl-xL, in a PI 3-kinase- and MAP kinase-dependent manner. (C) 1998 Academic Press.