The Orphan Nuclear Receptor NR4A1 Protects Pancreatic β-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis.
Bottom Line: This conclusion was further confirmed by experiments exploiting siRNA to knockdown NR4A1 expression in MIN6 cells or exploiting NR4A1 knock-out mice.NR4A1 overexpression in MIN6 cells or mouse islets resulted in Survivin up-regulation.In conclusion, NR4A1 protects pancreatic β-cells against ER stress-mediated apoptosis by up-regulating Survivin expression and down-regulating CHOP expression, which we termed as "positive and negative regulation."
Affiliation: From the The Department of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.Show MeSH
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Mentions: To investigate whether a lack of NR4A1 effects β-cell death under ER stress conditions in mouse islets, we purified islets from global NR4A1 knock-out mice (KO) and wild-type mice (WT). First, we did genotype identification by RT-PCR to amplify the full-length cDNA using a specific pair of primer and found there is no mRNA expression of NR4A1 in KO mice islets compared with WT mice (Fig. 8A). We treated the purified islets with TG or PA for 20 h, and TUNEL assays showed that the rate of apoptotic cells is much higher in KO islets than that in WT (Fig. 8, B and C). Moreover, we also overexpressed NR4A1 in islets from wild-type mice by viral infection with Ad-NR4A1. After infection for 48 h, the islets were treated with TG or PA for 20 h, and TUNEL assays showed that the rate of apoptotic cells is much lower in NR4A1 overexpressed islets than that of control islets infected with control virus (Ad- GFP) (Fig. 8, D and E).
Affiliation: From the The Department of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.