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: Caspase3 activation is the canonical biological marker for apoptosis, and full-length Caspase3 is cleaved into a 17-kDa fragment during apoptosis. Therefore, we examined the levels of cleaved Caspase3 using Western blotting. We treated both NC and OV cells with TG or PA for various lengths of time, and Western blotting results revealed that OV cells had lower Caspase3 (17 kDa) levels compared with NC cells upon treatment with TG (Fig. 4A) or PA (Fig. 4B). Furthermore, Caspase3 (17 kDa) levels peaked later after TG treatment in OV cells than in NC cells. Moreover, transient overexpression NR4A1 with adenoviral infection in MIN6 cells resulted in reduced CHOP expression and decreased Caspase3 activation upon TG or PA treatment compared with control MIN6 cells infected with control adenovirus (Fig. 4, C and D).
Affiliation: From the The Department of Cell Biology, Shandong University School of Medicine, Jinan, China, 250012.