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Overexpression of the Nuclear Factor-{kappa}B subunit c-Rel protects against human islet cell death in vitro
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2009 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 297, no 5, E1067-E1077 p.Article in journal (Refereed) Published
Abstract [en]

The transcription factor nuclear factor  (NF)-kappa B is known to modulate rates of apoptosis and may therefore   play a role in the increased beta-cell death that occurs in type 1 and   type 2 diabetes. The aim of the present investigation was to study the   expression of NF-kappa B subunits in human islet cells and whether   overexpression of the NF-kappa B subunit c-Rel affects islet cell   survival. We detected expression of p65, Rel-B, p50, p105, p52, and the   ribosomal protein S3 (rpS3) in human islet cells. Among these, only p65   and rpS3 were translocated from the cytosolic to the nuclear fraction   in response to cytokines. Interestingly, rpS3 participated in p65   binding to the kappa B-element in gel shift analysis experiments. We   observed cytoplasmic c-Rel expression in vivo in 6J mice, and signs of   nuclear translocation in beta-cells of infiltrated nonobese diabetic   islets. Human islet cells were also dispersed by trypsin treatment and   transduced with a c-Rel adenoviral vector. This resulted in increased   expression of c-Rel and inhibitory factor kappa B, increased kappa   B-binding activity, and augmented protein levels of Bcl-X-L, c-IAP2,   and heat shock protein 72. c-Rel expression in human islet cells   protected against cytokine-induced caspase 3 activation and cell death.   c-Rel protected also against streptozotocin- and H2O2-induced cell   death, in both intact rat islets and human islet cells. We conclude   that rpS3 participates in NF-kappa B signaling and that a genetic   increase in the activity of the NF-kappa B subunit c-Rel results in   protection against cell death in human islets.

Place, publisher, year, edition, pages
2009. Vol. 297, no 5, E1067-E1077 p.
Keyword [en]
beta-cell apoptosis, ribosomal protein S3, Bcl-X-L, heat shock protein 72, caspase 3
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-120625DOI: 10.1152/ajpendo.00212.2009ISI: 000270990500012PubMedID: 19706790OAI: oai:DiVA.org:uu-120625DiVA: diva2:303681
Available from: 2010-03-15 Created: 2010-03-15 Last updated: 2010-07-01Bibliographically approved

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