Upregulation of immunoproteasomes by nitric oxide: Potential antioxidative mechanism in endothelial cells
Upregulation of immunoproteasomes by nitric oxide: Potential antioxidative mechanism in endothelial cells
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DOI：
10.1016/j.freeradbiomed.2005.10.052
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发表时间：
2006-03-15
影响因子：
7.4
通讯作者：
Kalyanaraman, B
中科院分区：
文献类型：
--
作者：
Kotamraju, S;Matalon, S;Kalyanaraman, B
一氧化氮(NO)- n中心点)可刺激蛋白酶体功能和泛素-蛋白酶体通路，改善氧化剂诱导的内皮细胞凋亡信号。了解(NO)-N-center dot刺激蛋白酶体并在内皮细胞中提供细胞保护的调节机制具有治疗意义，因为许多血管疾病的特征是(NO)-N-center dot的缺乏。在这里，我们报道了(NO)-N-center dot/cGMP/ camp诱导的免疫蛋白酶体亚基表达是蛋白酶体活性增加的原因。用蛋白激酶G和蛋白激酶A抑制剂预处理的细胞明显减弱(NO)- n中心点依赖性蛋白酶体的激活。结果表明，该信号机制增强了转录因子camp -应答元件结合蛋白的磷酸化，提高了camp -应答元件启动子活性，诱导了免疫蛋白酶体亚基（LMP2和LMP7）的表达。在转染反义LMP2和LMP7寡核苷酸的细胞中，(NO)- n中心点依赖性蛋白酶体活性被破坏。与野生型对照相比，iNOS（-/-）小鼠主动脉中LMP2和LMP7水平较低，提示内源性(NO)- n -中心点的产生在免疫蛋白酶体的基础调节中起重要作用。（NO）-N-center dot/cGMP/cAMP信号通路通过诱导免疫蛋白酶体减轻转铁蛋白铁介导的氧化应激和细胞凋亡。这些结果为(NO)- n中心点介导的免疫蛋白酶体信号通路在内皮细胞中提供细胞保护的调控机制提供了新的见解。(C) 2005爱思唯尔公司版权所有。
Nitric oxide ((NO)-N-center dot) was shown to stimulate the proteasomal function and the ubiquitin-proteasome pathway and to ameliorate endothelial apoptotic signaling induced by oxidants. Understanding the regulatory mechanisms by which (NO)-N-center dot stimulates proteasomes and affords cytoprotection in endothelial cells has therapeutic implications, as many vascular diseases are characterized by a deficiency in (NO)-N-center dot. Here we report that (NO)-N-center dot/cGMP/cAMP-induced immunoproteasome subunit expression is responsible for the increased proteasomal activities. Cells pretreated with protein kinase G and protein kinase A inhibitors markedly attenuated (NO)-N-center dot-dependent proteasome activation. Results show that the signaling mechanism enhanced the phosphorylation of the transcription factor cAMP-response element-binding protein, elevated the cAMP-response element-promoter activity and induced the expression of immunoproteasomal subunits (LMP2 and LMP7). (NO)-N-center dot-dependent proteasomal activity was abrogated in cells transfected with antisense LMP2 and LMP7 oligonucleotides. Lower levels of LMP2 and LMP7 were detected in aorta of iNOS(-/-) mice compared to wild-type controls, Suggesting that endogenous production of (NO)-N-center dot is important in the basal regulation Of immunoproteasome. The (NO)-N-center dot/cGMP/cAMP signaling pathway mitigates transferrin-iron-mediated oxidative stress and apoptosis through induction of immunoproteasomes. These results provide new insights on the regulatory mechanisms by which the (NO)-N-center dot-mediated immunoproteasome signaling pathway affords cytoprotection in endothelial cells. (C) 2005 Elsevier Inc. All rights reserved.