| Suppressor of cytokine signaling 1 inhibits apoptosis of islet grafts through caspase 3 and apoptosis-inducing factor pathways in rats. | |
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MedLine Citation:
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PMID: 20832564 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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A significant portion of pancreatic islet grafts can be destroyed by apoptosis, failing to engraft in the early period after transplantation. Recently, we observed that overexpression of suppressor of cytokine signaling 1 (SOCS1) in islet grafts achieved an antiapoptotic effect, prolonging graft survival in a rat transplant model. Caspase 3 is the central executioner caspase that is activated by upstream cascades in a caspase-dependent apoptosis pathway. Apoptosis inducing factor (AIF) is a key protein that can be released from mitochondria, translocating to the nucleus in the caspase-independent apoptosis pathway. In this study, we investigated whether these two pathways were involved in cytoprotection afforded by SOCS1 on islet grafts. We used a chimeric adenovirus vector (Ad5F35-SOCS1) to enhance SOCS1 expression in isolated Sprague-Dawley rat islets, which were transplanted into recipients experiencing streptozotocin-induced diabetes. We analyzed the expressions of active (cleaved) caspase 3 and AIF on islets. The Ad5F35-SOCS1-infected islets with higher SOCS1 expression showed decreased levels of active caspase 3 and intranuclear AIF after treatment with tumor necrosis factor-α and cycloheximide in vitro. The diabetic recipients transplanted with Ad5F35-SOCS1-infected islets showed longer periods of normoglycemia versus recipients transplanted with mock-infected islets (P < .05) due to prolonged graft survival. A histological analysis indicated that the Ad5F35-SOCS1-infected islet grafts displayed decreased caspase 3 activation and AIF translocation (to nucleus) in the early posttransplant period. These results demonstrated that the expression of SOCS1 in islet grafts protected them from apoptosis through caspase 3 dependent and AIF caspase-independent-pathways. |
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Authors:
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G J Suo; J Qin; C P Zhong; Z X Zhao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Transplantation proceedings Volume: 42 ISSN: 1873-2623 ISO Abbreviation: Transplant. Proc. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0243532 Medline TA: Transplant Proc Country: United States |
Other Details:
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Languages: eng Pagination: 2658-61 Citation Subset: IM |
Copyright Information:
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2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Surgery, Shanghai East Hospital, Tongji University, PR China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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