Downregulation of IRS-1 protein in thapsigargin-treated human prostate epithelial cells.
Downregulation of IRS-1 protein in thapsigargin-treated human prostate epithelial cells.
复制标题
毒胡萝卜素处理的人前列腺上皮细胞中 IRS-1 蛋白的下调。
DOI：
10.1016/s0014-4827(03)00286-6
复制
发表时间：
2003
影响因子：
3.7
通讯作者：
Sell,Christian
中科院分区：
文献类型：
--
作者：
Zhang,Hong;Hoff,Henry;Sell,Christian
Thapsigargin treatment of cultured cells leads to an increase in the intracellular calcium concentration, activation of calpain, and, in some cell types, apoptosis. Using a human prostate epithelial cell line that undergoes apoptosis in the presence of thapsigargin, we find decreased levels of IRS-1 protein levels during apoptosis. Inhibition of calpain prevents this decrease in IRS-1 protein; however, inhibitors of caspases or the proteasome are ineffective in maintaining IRS-1 levels. In terms of IGF-I-related second messenger proteins, the effect of thapsigargin is specific for IRS-1 since the protein levels of IGF-I receptor β-subunit, Akt, Erk, and Shc are not affected. In addition to preventing the reduction in IRS-1, treatment of cells with calpain inhibitor II prevents apoptosis in response to thapsigargin. Finally, IRS-1 and calpain can be identified in protein complexes isolated using IRS-1-specific antibodies, indicating that calpain can associate with either IRS-1 or one of the proteins present in protein complexes that contain IRS-1. In total, these results suggest that IRS-1 may be targeted for degradation by calpain during apoptosis.
