Search: (L773:0012 1797 OR L773:1939 327X) srt2:(2005-2009)
> (2005) >
Cytokines downregul...
Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells
-
Cardozo, AK (author)
-
Ortis, F (author)
-
Storling, J (author)
-
show more...
-
Feng, YM (author)
-
Rasschaert, J (author)
-
Tonnesen, M (author)
-
Van Eylen, F (author)
-
Mandrup-Poulsen, T (author)
-
Herchuez, A (author)
-
Eizirik, DL (author)
-
show less...
- American Diabetes Association, 2005
- 2005
- English.
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:2, s. 452-461
- Related links:
-
http://diabetes.diab...
-
show more...
-
http://kipublication...
-
https://doi.org/10.2...
-
show less...
Abstract
Subject headings
Close
- Cytokines and free radicals are mediators of β-cell death in type 1 diabetes. Under in vitro conditions, interleukin-1β (IL-1β) + γ-interferon (IFN-γ) induce nitric oxide (NO) production and apoptosis in rodent and human pancreatic β-cells. We have previously shown, by microarray analysis of primary β-cells, that IL-1β + IFN-γ decrease expression of the mRNA encoding for the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b (SERCA2b) while inducing expression of the endoplasmic reticulum stress–related and proapoptotic gene CHOP (C/EBP [CCAAT/enhancer binding protein] homologous protein). In the present study we show that cytokine-induced apoptosis and necrosis in primary rat β-cells and INS-1E cells largely depends on NO production. IL-1β + IFN-γ, via NO synthesis, markedly decreased SERCA2b protein expression and depleted ER Ca2+ stores. Of note, β-cells showed marked sensitivity to apoptosis induced by SERCA blockers, as compared with fibroblasts. Cytokine-induced ER Ca2+ depletion was paralleled by an NO-dependent induction of CHOP protein and activation of diverse components of the ER stress response, including activation of inositol-requiring ER-to-nucleus signal kinase 1α (IRE1α) and PRK (RNA-dependent protein kinase)-like ER kinase (PERK)/activating transcription factor 4 (ATF4), but not ATF6. In contrast, the ER stress–inducing agent thapsigargin triggered these four pathways in parallel. In conclusion, our results suggest that the IL-1β + IFN-γ–induced decrease in SERCA2b expression, with subsequent depletion of ER Ca2+ and activation of the ER stress pathway, is a potential contributory mechanism to β-cell death.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Diabetes
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
-
Cardozo, AK
-
Ortis, F
-
Storling, J
-
Feng, YM
-
Rasschaert, J
-
Tonnesen, M
-
show more...
-
Van Eylen, F
-
Mandrup-Poulsen, ...
-
Herchuez, A
-
Eizirik, DL
-
show less...
- Articles in the publication
-
Diabetes
- By the university
-
Karolinska Institutet