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PDGF Suppresses Oxidative Stress Induced Ca2+ Overload and Calpain Activation in Neurons
- Source :
- Oxidative Medicine and Cellular Longevity, Oxidative Medicine and Cellular Longevity, Vol 2013 (2013)
- Publication Year :
- 2013
- Publisher :
- Hindawi Publishing Corporation, 2013.
-
Abstract
- Oxidative stress is crucially involved in the pathogenesis of neurological diseases such as stroke and degenerative diseases. We previously demonstrated that platelet-derived growth factors (PDGFs) protected neurons from H2O2-induced oxidative stress and indicated the involvement of PI3K-Akt and MAP kinases as an underlying mechanism. Ca2+overload has been shown to mediate the neurotoxic effects of oxidative stress and excitotoxicity. We examined the effects of PDGFs on H2O2-induced Ca2+overload in primary cultured neurons to further clarify their neuroprotective mechanism. H2O2-induced Ca2+overload in neurons in a dose-dependent manner, while pretreating neurons with PDGF-BB for 24 hours largely suppressed it. In a comparative study, the suppressive effects of PDGF-BB were more potent than those of PDGF-AA. We then evaluated calpain activation, which was induced by Ca2+overload and mediated both apoptotic and nonapoptotic cell death. H2O2-induced calpain activation in neurons in a dose-dependent manner. Pretreatment of PDGF-BB completely blocked H2O2-induced calpain activation. To the best of our knowledge, the present study is the first to demonstrate the mechanism underlying the neuroprotective effects of PDGF against oxidative stress via the suppression of Ca2+overload and inactivation of calpain and suggests that PDGF-BB may be a potential therapeutic target of neurological diseases.
- Subjects :
- Aging
Programmed cell death
Article Subject
Excitotoxicity
Becaplermin
Intracellular Space
medicine.disease_cause
Biochemistry
Neuroprotection
Mice
medicine
Animals
Humans
lcsh:QH573-671
Ions
Neurons
Platelet-Derived Growth Factor
biology
lcsh:Cytology
Kinase
Calpain
Cell Biology
General Medicine
Hydrogen Peroxide
Proto-Oncogene Proteins c-sis
Cell biology
Enzyme Activation
Mice, Inbred C57BL
Oxidative Stress
Apoptosis
Immunology
biology.protein
Calcium
Platelet-derived growth factor receptor
Oxidative stress
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19420994 and 19420900
- Volume :
- 2013
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....1b660ff410a8b891202ab5e80f44eb66