Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein
Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein
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INS-1细胞过表达硫代氧化还蛋白的基因表达谱分析
DOI：
10.1016/j.bbrc.2005.08.161
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发表时间：
2005-10-28
影响因子：
3.1
通讯作者：
Shalev, A
中科院分区：
文献类型：
--
作者：
Minn, AH;Pise-Masison, CA;Shalev, A
硫氧还蛋白相互作用蛋白（TXNIP）在糖尿病中过度表达，对胰腺β细胞和心血管系统有有害影响。TXNIP是细胞氧化还原状态的调节剂，但也被认为是一种转录抑制因子。然而，TXNIP调控的基因和途径尚不清楚。因此，我们使用Affymetrix 230A大鼠芯片比较了过表达TXNIP的INS-1胰岛素瘤p细胞和过表达lacz的对照细胞的基因表达。用贝叶斯方法分析发现98个差异表达基因，其中90个下调，与TXNIP作为抑制因子的预测作用一致。使用PathwayAssist软件，我们发现受影响的基因参与细胞死亡/存活和胰岛素分泌，并通过实时RT-PCR和功能研究证实了这些发现。因此，除了调节细胞氧化还原外，TXNIP还调节整体基因转录，从而可能进一步促进β细胞死亡并损害胰岛素分泌。(c) 2005爱思唯尔公司版权所有。
Thioredoxin-interacting protein (TXNIP) is overexpressed in diabetes and has deleterious effects on pancreatic beta-cells and the cardiovascular system. TXNIP is a regulator of the cellular redox state, but has also been suggested to act as a transcriptional repressor. However, the genes and pathways regulated by TXNIP remain unknown. We therefore compared gene expression in INS-1 insulinoma P-cells overexpressing TXNIP and control LacZ-overexpressing cells using the Affymetrix 230A rat chip. Analysis with the Bayes methodology revealed 98 differentially expressed genes, 90 of which were down-regulated, consistent with the predicted role of TXNIP as a repressor. Using the PathwayAssist software, we found that affected genes were involved in cell death/survival and insulin secretion, and confirmed these findings by real-time RT-PCR and by functional studies. Thus, aside from regulating the cellular redox, TXNIP does modulate overall gene transcription and thereby may further enhance beta-cell death and impair insulin secretion. (c) 2005 Elsevier Inc. All rights reserved.