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C/EBP homologous pr...
C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in beta-cells
- Article/chapterEnglish2012
Publisher, publication year, extent ...
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2012-06-01
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Springer Science and Business Media LLC,2012
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-184626
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-184626URI
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https://doi.org/10.1038/cdd.2012.67DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic beta-cells. Pro-inflammatory cytokines are early mediators of beta-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in beta-cells, but the role for CHOP overexpression in cytokine-induced beta-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-kappa B (NF-kappa B) is a crucial transcription factor regulating beta-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-kappa B activity and expression of key NF-kappa B target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased I kappa B degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting beta-cell death: (1) CHOP directly contributes to cytokine-induced beta-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-kappa B activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis. Cell Death and Differentiation (2012) 19, 1836-1846; doi:10.1038/cdd.2012.67; published online 1 June 2012
Subject headings and genre
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CHOP
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Bcl-2 proteins
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ER stress
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apoptosis
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pancreatic beta-cell
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inflammation
Added entries (persons, corporate bodies, meetings, titles ...)
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Fukaya, M.
(author)
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Nogueira, T. C.
(author)
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Delaroche, D.
(author)
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Welsh, NilsUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)nilswels
(author)
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Marselli, L.
(author)
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Marchetti, P.
(author)
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Haefliger, J. A.
(author)
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Eizirik, D. L.
(author)
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Cardozo, A. K.
(author)
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Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Related titles
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In:Cell Death and Differentiation: Springer Science and Business Media LLC19:11, s. 1836-18461350-90471476-5403
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Allagnat, F.
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Fukaya, M.
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Nogueira, T. C.
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Delaroche, D.
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Welsh, Nils
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Marselli, L.
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Marchetti, P.
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Haefliger, J. A.
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Eizirik, D. L.
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Cardozo, A. K.
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Cell Death and D ...
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Uppsala University