Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death

Morishita, Emi; Masuda, Seiji; Nagao, Masaya; Yasuda, Yoshiko; Sasaki, Ryuzo

doi:10.1016/s0306-4522(96)00306-5

Cited by 610 publications

(452 citation statements)

References 52 publications

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“…Studies in vitro provided informations related to the molecular pathways involved in EPO action. These data showed that EPO may have a direct protective role against a variety of neurotoxic insults, such as hypoxic conditions [11] , glutamate toxicity [12] , free-radical injury [13] , and exposure to neurotoxicants [14] . In addition, EPO receptor is abundantly expressed in adult dopaminergic neurons [15] , suggesting a direct effect of EPO on neurons.…”

Section: Discussionmentioning

confidence: 88%

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Shang

Sun

et al. 2007

Neurosci. Bull.

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Objective The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP + )-induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated. Methods PC12 cells impaired by MPP + were used as the cell model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of the PC12 cells exposed to gradient concentrations of EPO, and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was used to analyze the apoptosis ratio of PC12 cells. The expression of Bcl-2 and Bax in PC12 cells were examined by Western blot, and the reactive oxygen species (ROS), the mitochondrial transmembrane potential and the activity of caspase-3 in each group were detected by spectrofluorometer. Results Treatment of PC12 cells with MPP + caused the loss of cell viability, which may be associated with the elevation in apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. It was also shown that MPP + significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, EPO significantly reversed these responses and had the maximum protective effect at 1 U/mL. Conclusion The inhibitive effect of EPO on the MPP + -induced cytotoxicity may be ascribed to its anti-oxidative property and anti-apoptotic activity, and EPO may provide a useful therapeutic strategy for treatment of neurodegenerative diseases such as Parkinson's disease.

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Section: Discussionmentioning

confidence: 88%

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Shang

Sun

et al. 2007

Neurosci. Bull.

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“…21,23,26,[32][33][34] EPO-R have been identified in the hippocampus, amygdala, and temporal cortex of the human brain, where endogenous EPO production by astrocytes is induced in an oxygen-dependent manner and may have a neuroprotective function. 20 -24,32 Recent work suggests that EPO may play an important role in enhancing neuronal cell survival under sublethal hypoxicischemic insult by mediating cellular CA 2ϩ influx, thus counteracting glutamate toxicity, 23,25 suppressing the nitric oxide-induced formation of free radicals, antagonizing free radical toxicity, 33 and preventing cell death by inhibiting apoptosis. 6 EPO and EPO-R have been identified on the spinal cords of human fetuses 5 and in the CSF of preterm and term neonates in which therapy with rHuEPO had no effect on the CSF concentration of EPO.…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopmental Outcome of Prematurely Born Children Treated With Recombinant Human Erythropoietin in Infancy

et al. 1999

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“…2B). Erythropoietin reduces neuronal death with OGD, 86 glutamate toxicity, 91 and NO-induced cell death. 92 Astrocytes contribute to the EPO-mediated neuroprotection, as demonstrated by experiments in which conditioned media taken from hypoxic astrocyte cultures is protective to neurons exposed to OGD.…”

Section: Astrocytes and Epo As A Neuroprotectantmentioning

confidence: 99%

Targeting Astrocytes for Stroke Therapy

2010

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Summary: Stroke remains a major health problem and is a leading cause of death and disability. Past research and neurotherapeutic clinical trials have targeted the molecular mechanisms of neuronal cell death during stroke, but this approach has uniformly failed to reduce stroke-induced damage or to improve functional recovery. Beyond the intrinsic molecular mechanisms inducing neuronal death during ischemia, survival and function of astrocytes is absolutely required for neuronal survival and for functional recovery after stroke. Many functions of astrocytes likely improve neuronal viability during stroke. For example, uptake of glutamate and release of neurotrophins enhances neuronal viability during ischemia. Under certain conditions, however, astrocyte function may compromise neuronal viability. For example, astrocytes may produce inflammatory cytokines or toxic mediators, or may release glutamate. The only clinical neurotherapeutic trial for stroke that specifically targeted astrocyte function focused on reducing release of S-100␤ from astrocytes, which becomes a neurotoxin when present at high levels. Recent work also suggests that astrocytes, beyond their influence on cell survival, also contribute to angiogenesis, neuronal plasticity, and functional recovery in the several days to weeks after stroke. If these delayed functions of astrocytes could be targeted for enhancing stroke recovery, it could contribute importantly to improving stroke recovery. This review focuses on both the positive and the negative influences of astrocytes during stroke, especially as they may be targeted for translation to human trials.

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Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death

Cited by 610 publications

References 52 publications

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells

Neurodevelopmental Outcome of Prematurely Born Children Treated With Recombinant Human Erythropoietin in Infancy

Targeting Astrocytes for Stroke Therapy

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