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Increased Hsp70 expression attenuates cytokine-induced cell death in islets of Langerhans from Shb knockout mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Hannover University.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 387, no 3, 553-557 p.Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes may depend on cytokine-induced beta-cell death and therefore the current investigation was performed in order to elucidate this response in Shb-deficient islets. A combination of interleukin-1beta and interferon-gamma caused a diminished beta-cell death response in Shb null islets. Furthermore, the induction of an unfolded protein response (UPR) by adding cyclopiazonic acid did not increase cell death in Shb-deficient islets, despite simultaneous expression of UPR markers. The heat-shock protein Hsp70 was more efficiently induced in Shb knockout islets, providing an explanation for the decreased susceptibility of Shb-deficient islets to cytokines. It is concluded that islets deficient in the Shb protein are less susceptible to cytotoxic conditions, and that this partly depends on their increased ability to induce Hsp70 under such circumstances. Interference with Shb signaling may provide means to improve beta-cell viability under conditions of beta-cell stress.

Place, publisher, year, edition, pages
2009. Vol. 387, no 3, 553-557 p.
Keyword [en]
beta-Cells, Cytokines, Cell death, Shb, Unfolded protein response, Hsp70
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-123108DOI: 10.1016/j.bbrc.2009.07.051ISI: 000269137800026PubMedID: 19615333OAI: oai:DiVA.org:uu-123108DiVA: diva2:312389
Available from: 2010-04-23 Created: 2010-04-23 Last updated: 2017-12-12Bibliographically approved

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Mokhtari, DariushÅkerblom, BjörnWang, XuanOlerud, JohanWelsh, NilsWelsh, Michael

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