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Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival
Abstract
Insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) are trophic factors required for the viability and normal functions of various neuronal cells. However, the detailed intracellular mechanism(s) involved in these effects in neuronal cells remains to be fully elucidated. In present study, the respective intracellular signaling pathway induced by IGF-1 and BDNF and their possible role in neuronal survival were investigated. Both IGF-1 and BDNF protected hippocampal neurons from serum deprivation-induced death with IGF-1 apparently being more potent. Western blot analyses showed that both IGF-1 and BDNF induced the activation of the phosphatidylinositide 3 kinase (PI3)/Akt (protein kinase B) kinase and the mitogen-activated protein kinase (MAPK) pathways. The phosphorylation of Akt and its downstream target, FKHRL1, induced by IGF-1 was rapid and sustained while that of MAPK was transient. The reverse situation was observed for BDNF. Moreover, IGF-1 potently induced the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with PI3 kinase while BDNF was weak in these assays. In contrast, the tyrosine phosphorylation of Shc proteins was dramatically stimulated by BDNF, with IGF-1 having only a minimal effect. Most interestingly, only the inhibitor of the PI3K/Akt pathway, LY294002, was able to block the survival effects of both IGF-1 and BDNF; an inhibitor of the MAPK pathway inhibitor, PD98059, being ineffective. Taken together, these data reveal that the survival properties of both IGF-1 and BDNF against serum deprivation are mediated by the activation of the PI3K/Akt, but not the MAPK, pathway in hippocampal neurons.
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“As previously mentioned, the key element of neurotrophin-related neuroprotection is the IP3/Akt kinase pathway [186].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [186]
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Metadata
- Authors
- Zheng, W., & Quirion, R.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-04-13
- Volume
- 89
- Issue
- 4
- Pages
- 844-852
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2031452891
- Cited by
- 225
- References
- 44
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 18 · 2020: 8 · 2019: 12 · 2018: 3 · 2017: 9 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 17 · 2012: 19
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin-like growth factor I, brain-derived neurotrophic factor, hippocampal neurons, neuronal survival, PI3K/Akt signaling, MAPK signaling, serum deprivation, Akt phosphorylation, FKHRL1, IRS-1, Shc, trophic factors, LY294002, PD98059
- MeSH terms
- Src Homology 2 Domain-Containing, Transforming Protein 1, Animals, Cell Survival, Cells, Cultured, Enzyme Inhibitors, Hippocampus, Insulin-Like Growth Factor I, Neurons, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins, Signal Transduction, Culture Media, Serum-Free, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Brain-Derived Neurotrophic Factor, Phosphatidylinositol 3-Kinases, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Rats, Insulin Receptor Substrate Proteins, Shc Signaling Adaptor Proteins
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