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Astroglial cytoprotection by erythropoietin pre‐conditioning: implications for ischemic and degenerative CNS disorders
Author(s) -
Diaz Zuanel,
Assaraf Michael I.,
Miller Wilson H.,
Schipper Hyman M.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03038.x
Subject(s) - cytoprotection , erythropoietin , neuroprotection , oxidative stress , nitric oxide , pharmacology , heme oxygenase , arsenic trioxide , medicine , erythropoietin receptor , apoptosis , endocrinology , biology , heme , biochemistry , enzyme
Erythropoietin (Epo) is a glycoprotein secreted by the kidney in response to hypoxia that stimulates erythropoiesis through interaction with cell surface Epo receptors. Pre‐treatment with Epo has been shown to protect neurons in models of ischemic injury. The mechanism responsible for this neuroprotection and the effects of Epo on astroglial and other non‐neuronal cell populations remain unknown. In the present study, we determined whether Epo pre‐treatment protects neonatal rat astrocytes from apoptotic cell death resulting from treatment with nitric oxide, staurosporine (STS) and arsenic trioxide and possible mechanisms mediating Epo‐related cytoprotection. Epo (5–20 U/mL) significantly attenuated multiple hallmarks of apoptotic cell death in astroglia exposed to nitric oxide and STS but not arsenic trioxide. Epo (20 U/mL) induced mild oxidative stress as shown by increases in heme oxygenase (HO)‐1 mRNA and protein expression that could be suppressed by antioxidant coadministration. Moreover, coincubation with tin‐mesoporphyrin, a competitive inhibitor of HO activity, abrogated the cytoprotective effects of Epo (20 U/mL) in the face of STS treatment. Thus, induction of the ho‐ 1 gene may contribute to the glioprotection accruing from high‐dose Epo exposure. Epo may augment astroglial resistance to certain chemical stressors by oxidative stress‐dependent and ‐independent mechanisms.