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Journal of Neuroscience, Vol 15, 7095-7104, Copyright © 1995 by Society for Neuroscience
PDGFs protect hippocampal neurons against energy deprivation and oxidative injury: evidence for induction of antioxidant pathways
B Cheng and MP Mattson
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA.
Platelet-derived growth factors (PDGFs) and PDGF receptors are expressed in
brain, where their functions are largely unknown. We tested the hypothesis
that PDGFs play a role in promoting the survival of neurons exposed to
metabolic and oxidative insults. Exposure of rat and mouse hippocampal cell
cultures to glucose-deficient medium or the hydroxyl radical-promoting
agent FeSO4 resulted in progressive neuronal loss. Pretreatment of cultures
with PDGF-AA or PDGF-BB resulted in highly significant attenuation of
glucose deprivation- and FeSO4- induced neuronal degeneration. In each
injury paradigm the neuroprotective actions of the PDGFs were concentration
dependent (3- 100 ng/ml). In the case of glucose deprivation, significant
protection was seen when cells were exposed to PDGFs prior to, or up to 8
hr following, the onset of glucose deprivation. Pretreatment with PDGFs was
required for protection against FeSO4-induced oxidative injury. Western
blot and immunocytochemical analyses demonstrated that cultured embryonic
hippocampal neurons expressed both PDGF alpha- and beta- receptors. PDGFs
induced tyrosine phosphorylation of several proteins including a band at
180 kDa, the molecular weight of PDGF receptors. Induction of peroxide
accumulation in neurons by FeSO4 was attenuated in cultures pretreated with
PDGFs, suggesting that PDGFs enhanced cellular antioxidant mechanisms.
Measurements of anti-oxidant enzyme activities in control and PDGF-treated
cultures showed that both PDGF- AA and PDGF-BB increased both catalase and
glutathione peroxidase activities, and PDGF-AA also increased superoxide
dismutase activities. These findings suggest that PDGFs, which are widely
expressed in brain and induced in response to injury, may play roles in
protecting neurons against metabolic and oxidative insults.
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