Regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) expression by interleukin-1β in pancreatic βcells

Chunli Shao, Michael C. Lawrence, Melanie H. Cobb

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Apoptosis contributes to immune-mediated pancreatic βcell destruction in type I diabetes. Exposure of β cells to interleukin-1β (IL-1β) causes endoplasmic reticulum stress and activates proapoptotic networks. Here, we show that nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways regulate the expression of CCAAT/enhancer-binding protein homologous protein (CHOP), which mediates endoplasmic reticulum stress-induced apoptosis. Both CHOP mRNA and protein increase in β cells treated with IL-1β. In addition, prolonged exposure to high glucose further increases IL-1β-triggered CHOP expression. IL-1β also causes increased expression of C/EBP-βand a reduction of MafA, NFATc2, and Pdx-1 expression in β cells. Inhibition of the NF-κB and MAPK signaling pathways differentially attenuates CHOP expression. Knocking down CHOP by RNA interference protects β cells from IL-1β-induced apoptosis. These studies provide direct mechanistic links between cytokine-induced signaling pathways and CHOP-mediated apoptosis of β cells.

Original languageEnglish (US)
Pages (from-to)19710-19719
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number26
DOIs
StatePublished - Jun 25 2010

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CCAAT-Enhancer-Binding Proteins
Interleukin-1
Apoptosis
Mitogen-Activated Protein Kinases
Proteins
Endoplasmic Reticulum Stress
Medical problems
RNA Interference
Type 1 Diabetes Mellitus
RNA
Cytokines
Glucose
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) expression by interleukin-1β in pancreatic βcells. / Shao, Chunli; Lawrence, Michael C.; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 285, No. 26, 25.06.2010, p. 19710-19719.

Research output: Contribution to journalArticle

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