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Journal article
Activation of proteasome by insulin-like growth factor-I may enhance clearance of oxidized proteins in the brain
Mechanisms of ageing and development, v 130(11-12), pp 793-800
01 Nov 2009
PMID: 19896963
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The insulin-like growth factor type I (IGF-I) plays an important role in neuronal physiology. Reduced IGF-I levels are observed during aging and this decrease may be important to age-related changes in the brain. We studied the effects of IGF-I on total protein oxidation in brain tissues and in cell cultures. Our results indicate that in frontal cortex the level of oxidized proteins is significantly reduced in transgenic mice designed to overproduce IGF-I compared with wild-type animals. The frontal cortex of IGF-I-overproducing mice exhibited high chymotrypsin-like activity of the 20S and 26S proteasomes. The proteasome can also be activated in response to IGF-I in cell cultures. Kinetic studies revealed peak activation of the proteasome within 15 min following IGF-I stimulation. The effects of IGF-I on proteasome were not observed in R- cells lacking the IGF-I receptor. Experiments using specific kinase inhibitors suggested that activation of proteasome by IGF-I involves phosphatidyl inositol 3-kinase and mammalian target of rapamycin signaling. IGF-I also attenuated the increase in protein carbonyl content induced by proteasome inhibition. Thus, appropriate levels of IGF-I may be important for the elimination of oxidized proteins in the brain in a process mediated by activation of the proteasome. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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Details
- Title
- Activation of proteasome by insulin-like growth factor-I may enhance clearance of oxidized proteins in the brain
- Creators
- Elizabeth Crowe - Drexel UniversityChristian Sell - Drexel UniversityJeff D. Thomas - Drexel UniversityGregg J. Johannes - Drexel UniversityClaudio Torres - Drexel University
- Publication Details
- Mechanisms of ageing and development, v 130(11-12), pp 793-800
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- R01AG022443 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) AG022443; AG022443-S1 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Neurobiology and Anatomy; Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000273864900011
- Scopus ID
- 2-s2.0-71849109181
- Other Identifier
- 991019168412004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell Biology
- Geriatrics & Gerontology