Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Diabetes |
| Vol/bind | 54 |
| Udgave nummer | 2 |
| Sider (fra-til) | 452-61 |
| Antal sider | 9 |
| ISSN | 0012-1797 |
| Status | Udgivet - 2005 |
Bibliografisk note
Keywords: Animals; Base Sequence; Calcium; Calcium-Transporting ATPases; Cytokines; DNA Primers; Endoplasmic Reticulum; Gene Expression Regulation, Enzymologic; Islets of Langerhans; Oxidative Stress; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sarcoplasmic Reticulum; ThapsigarginCitationsformater
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
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, Alessandra K; Ortis, Fernanda; Storling, Joachim; Feng, Ying-Mei; Rasschaert, Joanne; Tonnesen, Morten; Van Eylen, Françoise; Mandrup-Poulsen, Thomas; Herchuelz, André; Eizirik, Décio L.
I: Diabetes, Bind 54, Nr. 2, 2005, s. 452-61.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - 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.
AU - Cardozo, Alessandra K
AU - Ortis, Fernanda
AU - Storling, Joachim
AU - Feng, Ying-Mei
AU - Rasschaert, Joanne
AU - Tonnesen, Morten
AU - Van Eylen, Françoise
AU - Mandrup-Poulsen, Thomas
AU - Herchuelz, André
AU - Eizirik, Décio L
N1 - Keywords: Animals; Base Sequence; Calcium; Calcium-Transporting ATPases; Cytokines; DNA Primers; Endoplasmic Reticulum; Gene Expression Regulation, Enzymologic; Islets of Langerhans; Oxidative Stress; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sarcoplasmic Reticulum; Thapsigargin
PY - 2005
Y1 - 2005
N2 - Cytokines and free radicals are mediators of beta-cell death in type 1 diabetes. Under in vitro conditions, interleukin-1beta (IL-1beta) + gamma-interferon (IFN-gamma) induce nitric oxide (NO) production and apoptosis in rodent and human pancreatic beta-cells. We have previously shown, by microarray analysis of primary beta-cells, that IL-1beta + IFN-gamma decrease expression of the mRNA encoding for the sarcoendoplasmic reticulum pump Ca(2+) 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 beta-cells and INS-1E cells largely depends on NO production. IL-1beta + IFN-gamma, via NO synthesis, markedly decreased SERCA2b protein expression and depleted ER Ca(2+) stores. Of note, beta-cells showed marked sensitivity to apoptosis induced by SERCA blockers, as compared with fibroblasts. Cytokine-induced ER Ca(2+) 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 1alpha (IRE1alpha) 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-1beta + IFN-gamma-induced decrease in SERCA2b expression, with subsequent depletion of ER Ca(2+) and activation of the ER stress pathway, is a potential contributory mechanism to beta-cell death.
AB - Cytokines and free radicals are mediators of beta-cell death in type 1 diabetes. Under in vitro conditions, interleukin-1beta (IL-1beta) + gamma-interferon (IFN-gamma) induce nitric oxide (NO) production and apoptosis in rodent and human pancreatic beta-cells. We have previously shown, by microarray analysis of primary beta-cells, that IL-1beta + IFN-gamma decrease expression of the mRNA encoding for the sarcoendoplasmic reticulum pump Ca(2+) 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 beta-cells and INS-1E cells largely depends on NO production. IL-1beta + IFN-gamma, via NO synthesis, markedly decreased SERCA2b protein expression and depleted ER Ca(2+) stores. Of note, beta-cells showed marked sensitivity to apoptosis induced by SERCA blockers, as compared with fibroblasts. Cytokine-induced ER Ca(2+) 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 1alpha (IRE1alpha) 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-1beta + IFN-gamma-induced decrease in SERCA2b expression, with subsequent depletion of ER Ca(2+) and activation of the ER stress pathway, is a potential contributory mechanism to beta-cell death.
M3 - Journal article
C2 - 15677503
VL - 54
SP - 452
EP - 461
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 2
ER -