Sökning: onr:"swepub:oai:DiVA.org:uu-184626" >
C/EBP homologous pr...
-
Allagnat, F.
(författare)
C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in beta-cells
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
-
2012-06-01
-
Springer Science and Business Media LLC,2012
-
printrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-184626
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-184626URI
-
https://doi.org/10.1038/cdd.2012.67DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
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
Ämnesord och genrebeteckningar
-
CHOP
-
Bcl-2 proteins
-
ER stress
-
apoptosis
-
pancreatic beta-cell
-
inflammation
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Fukaya, M.
(författare)
-
Nogueira, T. C.
(författare)
-
Delaroche, D.
(författare)
-
Welsh, NilsUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)nilswels
(författare)
-
Marselli, L.
(författare)
-
Marchetti, P.
(författare)
-
Haefliger, J. A.
(författare)
-
Eizirik, D. L.
(författare)
-
Cardozo, A. K.
(författare)
-
Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Cell Death and Differentiation: Springer Science and Business Media LLC19:11, s. 1836-18461350-90471476-5403
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Allagnat, F.
-
Fukaya, M.
-
Nogueira, T. C.
-
Delaroche, D.
-
Welsh, Nils
-
Marselli, L.
-
visa fler...
-
Marchetti, P.
-
Haefliger, J. A.
-
Eizirik, D. L.
-
Cardozo, A. K.
-
visa färre...
- Artiklar i publikationen
-
Cell Death and D ...
- Av lärosätet
-
Uppsala universitet