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Activation of the insulin‐like growth factor‐I receptor inhibits tumor necrosis factor‐induced cell death

Activation of the insulin‐like growth factor‐I receptor inhibits tumor necrosis factor‐induced... 10.1002/(SICI)1097-4652(199609)168:3<499::AID-JCP2>3.3.CO;2-N The effect of insulin‐like growth factor (IGF) on tumor necrosis factor (TNF)‐induced cell killing was determined for mouse BALB/c3T3 fibroblasts in vitro. Cells maintained in 0.5% fetal bovine serum (FBS) were killed by TNF within 6 h in a concentration‐dependent manner, an effect that was prevented by IGF‐I. TNF‐induced cytotoxicity of 3T3 cells that overexpress the human IGF‐I receptor (p6 cells) was prevented by IGF‐I alone in the absence of serum. TNF‐induced cell death was associated with the morphologic features of apoptosis and the release of low‐molecular‐weight DNA, both of which were prevented by IGF‐I. Neither epidermal growth factor (EGF) nor platelet‐derived growth factor (PDGF) protected p6 cells from TNF‐induced apoptosis. The specific protective action of the IGF‐I receptor was demonstrated further by the marked sensitivity to TNF of embryo fibroblasts derived from mice with targeted disruption of the IGF‐I receptor (R cells) but not of fibroblasts derived from wild‐type littermates or R cells transfected with the cDNA for the human IGF‐I receptor. Cycloheximide or actinomycin D markedly reduced the protection offered by IGF‐I. IGF‐I protection of BALB/c3T3 cells persisted for up to 5 days in the presence of PDGF and EGF, whereas IGF‐I lost its effectiveness after 2 days in the absence of growth factors. IGF‐I did not prevent TNF‐induced release of arachidonic acid. The results demonstrate a specific role for the IGF‐I receptor in the protection against TNF cytotoxicity. This action of the IGF‐I receptor is mediated by protective cytosolic proteins that exhibit a high rate of turnover and whose levels are regulated principally by factors within serum other than IGF‐I. © 1996 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Physiology Wiley

Activation of the insulin‐like growth factor‐I receptor inhibits tumor necrosis factor‐induced cell death

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References (60)

Publisher
Wiley
Copyright
Copyright © 1996 Wiley‐Liss, Inc.
ISSN
0021-9541
eISSN
1097-4652
DOI
10.1002/(SICI)1097-4652(199609)168:3<499::AID-JCP2>3.0.CO;2-K
pmid
8816904
Publisher site
See Article on Publisher Site

Abstract

10.1002/(SICI)1097-4652(199609)168:3<499::AID-JCP2>3.3.CO;2-N The effect of insulin‐like growth factor (IGF) on tumor necrosis factor (TNF)‐induced cell killing was determined for mouse BALB/c3T3 fibroblasts in vitro. Cells maintained in 0.5% fetal bovine serum (FBS) were killed by TNF within 6 h in a concentration‐dependent manner, an effect that was prevented by IGF‐I. TNF‐induced cytotoxicity of 3T3 cells that overexpress the human IGF‐I receptor (p6 cells) was prevented by IGF‐I alone in the absence of serum. TNF‐induced cell death was associated with the morphologic features of apoptosis and the release of low‐molecular‐weight DNA, both of which were prevented by IGF‐I. Neither epidermal growth factor (EGF) nor platelet‐derived growth factor (PDGF) protected p6 cells from TNF‐induced apoptosis. The specific protective action of the IGF‐I receptor was demonstrated further by the marked sensitivity to TNF of embryo fibroblasts derived from mice with targeted disruption of the IGF‐I receptor (R cells) but not of fibroblasts derived from wild‐type littermates or R cells transfected with the cDNA for the human IGF‐I receptor. Cycloheximide or actinomycin D markedly reduced the protection offered by IGF‐I. IGF‐I protection of BALB/c3T3 cells persisted for up to 5 days in the presence of PDGF and EGF, whereas IGF‐I lost its effectiveness after 2 days in the absence of growth factors. IGF‐I did not prevent TNF‐induced release of arachidonic acid. The results demonstrate a specific role for the IGF‐I receptor in the protection against TNF cytotoxicity. This action of the IGF‐I receptor is mediated by protective cytosolic proteins that exhibit a high rate of turnover and whose levels are regulated principally by factors within serum other than IGF‐I. © 1996 Wiley‐Liss, Inc.

Journal

Journal of Cellular Physiology – Wiley

Published: Sep 1, 1996

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