Intracellular stress signaling pathways activated during human islet preparation and following acute cytokine exposure
Details
Serval ID
serval:BIB_A39BC6421470
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intracellular stress signaling pathways activated during human islet preparation and following acute cytokine exposure
Journal
Diabetes
ISSN
0012-1797 (Print)
Publication state
Published
Issued date
11/2004
Peer-reviewed
Oui
Volume
53
Number
11
Pages
2815-23
Language
english
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Abstract
Pancreatic islet transplantation may successfully restore normoglycemia in type 1 diabetic patients. However, successful grafting requires transplantation of a sufficient number of islets, usually requiring two or more donors. During the isolation process and following clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. Here, we have mapped the major intracellular stress-signaling pathways that may mediate human islet loss during isolation and following cytokine attack. We found that the isolation procedure potently recruits two pathways consisting of |mitogen-activated protein kinase kinase (MKK)7 --> Jun NH(2)-terminal kinase (JNK)/p38 --> c-fos| and the |nuclear factor-kappaB (NF-kappaB) --> iNOS| module. Cytokines activate the |NF-kappaB --> iNOS| and |MKK4/MKK3/6 --> JNK/p38| pathways without recruitment of c-fos. Culturing the islets for 48 h after isolation allows for the activated pathways to return to background levels, with expression of MKK7 becoming undetectable. These data indicate that isolation and cytokines recruit different death pathways. Therefore, strategies might be rationally developed to avoid possible synergistic activation of these pathways in mediating islet loss during isolation and following grafting.
Keywords
Apoptosis/drug effects
Base Sequence
Cytokines/*pharmacology
DNA Primers
Gene Expression Regulation/drug effects
Genes, fos/genetics
Humans
Interleukin-1/pharmacology
Islets of Langerhans/cytology/drug effects/*physiology
JNK Mitogen-Activated Protein Kinases/metabolism
MAP Kinase Kinase 4
Mitogen-Activated Protein Kinase Kinases/metabolism
RNA, Messenger/genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
p38 Mitogen-Activated Protein Kinases/metabolism
Pubmed
Web of science
Create date
25/01/2008 16:18
Last modification date
20/08/2019 15:09