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: We treated NC and OV cells with TG and harvested the cells at various time points for RNA purification or protein extraction. qPCR results showed that there was no significant difference in XBP1 splicing between NC and OV cells (Fig. 5A), but activating transcription factor 4 (ATF4) and CHOP mRNA levels were decreased in OV cells compared with NC cells (Fig. 5, B and C). CHOP protein expression also decreased in OV cells upon TG treatment compared with NC cells (Fig. 5D). Western blotting results show that phosphorylated eif2α, a subunit of eukaryotic translation initiation factor 2α, decreased substantially in OV cells compared with NC cells at 12 h and 24 h (Fig. 5E).
Affiliation: From the The Department of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.