Metadata of CSIR Papers
View Archive Info| Field | Value | |
| Creator |
Verma, G
Datta, M |
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| Subject |
Biochemistry & Molecular Biology; Cell Biology
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| Description |
The proinflammatory cytokine, IL-1 beta (Interleukin-1 beta) is a significant determinant of pancreatic apoptosis and cell death that are common characteristics during diabetes. Using human derived pancreatic MIA PaCa-2 cells, we describe one of the underlying molecular mechanisms behind this observation. Incubation of these cells with IL-1 beta at doses from 0.5 to 3.0 ng/ml caused significant cell death at 36 h. This was accompanied with marked increases in JNK and p38 phosphorylation together with increased levels of the endoplasmic reticulum (ER) stress markers, namely BiP, CHOP, GADD34, ATF4 and sXBP1. IL-1 beta also led to increased phosphorylation of eIF2 alpha and all these events could be prevented by pretreatment with the JNK inhibitor, SP600125. A time course study indicated that while IL-1 beta mediated JNK phosphorylation was induced as early as 2 h of IL-1 beta treatment, induction of the ER stress markers was evident at later time points. IL-1 beta stimulated JNK phosphorylation was observed even in the presence of the ER stress inhibitor, 4-phenyl butyrate and the decrease in cell viability was significantly prevented in the presence of the JNK inhibitor. All these suggest that JNK activation is a pre-requisite for ER stress induction and cell death. Reports till date have consistently demonstrated JNK activation as a consequence of ER stress induction by IL-1 beta in the pancreas. We show here for the first time that the activation of JNK by IL-1 beta is a prelude to the subsequent induction of ER stress and cell death. These therefore suggest that the JNK-ER stress axis is critical in deciding the decreased survival status by IL-1 beta in MIA PaCa-2 cells.
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| Publisher |
SPRINGERDORDRECHTVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
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| Date |
2011-09-20T12:07:07Z
2011-09-20T12:07:07Z 2010 |
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| Type |
Article
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| Identifier |
APOPTOSIS
1360-8185 http://hdl.handle.net/123456789/13112 |
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| Language |
English
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