Involvement of Alpha1beta1 Integrin in Insulin-like Growth Factor-1-mediated Protection of Pc12 Neuronal Processes from Tumor Necrosis Factor-alpha-induced Injury.
From: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA.
Journal of neuroscience research
- Publish Date: Jan 2006
- ISSN: 0360-4012
- Volume: 83
- Issue: 1
- Pages: 7-18
- Medium: Print
- Language: English
- Citation (JAMA): Wang Jin Ying, Grabacka Maja, Marcinkiewicz Cezary, et al. Involvement of Alpha1beta1 Integrin in Insulin-like Growth Factor-1-mediated Protection of Pc12 Neuronal Processes from Tumor Necrosis Factor-alpha-induced Injury.. J. Neurosci. Res. Jan 2006;83:7-18
Abstract
Insulin-like growth factor 1 receptor (IGF-1R) supports neuronal survival against a wide variety of insults. This includes tumor necrosis factor-alpha (TNFalpha)-mediated neuronal damage, which represents one of the factors suspected to play a role in HIV-associated dementia (HAD). PC12 neurons engineered to express human IGF-1R (PC12/IGF-1R) maintain neuronal processes on collagen IV for several weeks. However, prolonged treatment with TNFalpha caused degeneration of neuronal processes, with no apparent signs of apoptosis. In this process, TNFalpha did not affect IGF-1-mediated phosphorylation of IRS-1, IRS-2, Akt, or Erks. In addition, PC12/IGF-1R cells were found to express predominantly alpha1beta1 integrin, which has high affinity to collagen IV. The treatment of PC12/IGF-1R neurons with a specific alpha1beta1 integrin inhibitor, obtustatin, also caused loss of neuronal processes, accompanied by a quick cell detachment and extensive apoptosis. In the presence of IGF-1, both TNFalpha-induced and obtustatin-induced degeneration of neuronal processes were effectively inhibited. Furthermore, TNFalpha-mediated neuronal degeneration correlated with decreased attachment of PC12/IGF-1R cells to collagen IV and with a reduced level of alpha1beta1 integrin, consistent with a role for this surface protein in the maintenance of neuronal processes. Thus the neuroprotective effects of IGF-1 are not restricted to its antiapoptotic properties but also involve an additional neuroprotective mechanism, by which IGF-1 counteracts the negative effect of TNFalpha on alpha1beta1 integrin-mediated attachment to collagen IV.
Mesh Headings (Keywords): Animals, Antineoplastic Agents, Apoptosis, Blotting, Western, Cell Adhesion, Cell Differentiation, Disintegrins, Fluorescent Antibody Technique, Immunoprecipitation, Insulin-Like Growth Factor I, Integrin alpha1beta1, PC12 Cells, Phosphorylation, Platelet Aggregation Inhibitors, Rats, Signal Transduction, Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 16307448
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