The reductase NCB5OR is responsive to the redox status in beta-cells and is not involved in the ER stress response.
The reductase NCB5OR is responsive to the redox status in beta-cells and is not involved in the ER stress response.
复制标题
还原酶 NCB5OR 对 β 细胞中的氧化还原状态有反应,但不参与 ER 应激反应。
DOI:
10.1042/bj20061859
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发表时间:
2007
期刊:
影响因子:
--
通讯作者:
Bunn,HFranklin
中科院分区:
文献类型:
--
作者:
Larade,Kevin;Jiang,Zhi-gang;Dejam,Andre;Zhu,Hao;Bunn,HFranklin
The novel reductase NCB5OR (NADPH cytochromeb5oxidoreductase) resides in the ER (endoplasmic reticulum) and may protect cells against ER stress. Levels of BiP (immunoglobulin heavy-chain-binding protein), CHOP (CCAAT/enhancer-binding protein homologous protein) and XBP-1 (X-box-binding protein-1) did not differ in WT (wild-type) and KO (Ncb5or-null) tissues or MEFs (mouse embryonic fibroblasts), and XBP-1 remained unspliced. MEFs treated with inducers of ER stress demonstrated no change inNcb5orexpression and expression of ER-stress-induced genes was not enhanced. Induction of ER stress in β-cell lines did not changeNcb5orexpression or promoter activity. Transfection withNcb5or-specific siRNA (small interfering RNA) yielded similar results. Microarray analysis of mRNA from islets and liver of WT and KO animals revealed no significant changes in ER-stress-response genes. Induction of oxidative stress in βTC3 cells did not alterNcb5ormRNA levels or promoter activity. However, KO islets were more sensitive to streptozotocin when compared with WT islets. MEFs incubated with nitric oxide donors showed no difference in cell viability or levels of nitrite produced. No significant differences in mRNA expression of antioxidant enzymes were observed when comparing WT and KO tissues; however, microarray analysis of islets indicated slightly enhanced expression of some antioxidant enzymes in the KO islets. Short-term tBHQ (t-butylhydroquinone) treatment increasedNcb5orpromoter activity, although longer incubation times yielded a dose-dependent decrease in activity. This response appears to be due to a consensus ARE (antioxidant-response element) present in theNcb5orpromoter. In summary, NCB5OR does not appear to be involved in ER stress, although it may be involved in maintaining or regulating the redox status in β-cells.