Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production

Genç, Şermin; Kuralay, Filiz; Akhisaroğlu, Mustafa; Fadiloglu, S.; Yörükoğlu, Kutsal; Fadiloğlu, Meral; Güre, Ataman

doi:10.1016/s0304-3940(00)01716-x

Cited by 122 publications

(75 citation statements)

References 12 publications

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“…In addition, EPO receptor is abundantly expressed in adult dopaminergic neurons [15] , suggesting a direct effect of EPO on neurons. EPO can also protect dopaminergic neurons against the neurotoxicities of MPTP and 6-hydroxydopamine, and significantly reverse the corresponding behavioral deficits in mice [8,10] . The protection of EPO in the central nervous system is mediated by a series of cellular pathways that maintain intricate links between one another.…”

Section: Discussionmentioning

confidence: 99%

“…It has been also reported that EPO displays efficient neuroprotective properties in a spectrum of different animal models, including ischemia/hypoxia, excitotoxic paradigms, traumatic brain and spinal cord injury, and retina/optic nerve damage in inflammatory/auto-immunological diseases [7] . Recent studies have revealed a possible protective role of EPO in Parkinson's disease [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

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促红细胞生成素对1-甲基-4-苯基吡啶损伤的 Pc12 细胞的保护作用

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: 99%

Section: Introductionmentioning

confidence: 99%

促红细胞生成素对1-甲基-4-苯基吡啶损伤的 Pc12 细胞的保护作用

Shang

Sun

et al. 2007

Neurosci. Bull.

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“…Slight improvements in functional outcome with variable efficacy to reduce histological damage have indeed been reported in models of Parkinson disease and amyotrophic lateral sclerosis (ALS) in which these compounds presumably act by inducing anti-oxidant enzymes, inhibiting apoptosis, and stimulating axonal regeneration. [112][113][114][115] Furthermore, EPO improved graft survival of embryonic ventral mesencephalic dopamine neurons when transplanted into the striatum of 6-hydroxy-dopamine lesioned rats. 116 However, treatment with asialo-EPO failed to reduce cell death or modify disease progression in a mouse model of Huntington's disease.…”

Section: Neurodegenerationmentioning

confidence: 99%

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

et al. 2009

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Summary:The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, antiapoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.

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“…Accumulating evidence has shown that EPO protein and EPO receptors (EPORs) exist in CNS neurons. 1,2 EPO has been found to protect dopaminergic (DA) neurons from experimental insults and druginduced degeneration, 1,[3][4][5][6] suggesting its therapeutic potential for Parkinson's disease (PD). In our previous study with EPO protein infusions, although intrastriatal delivery was protective, systemic administration of EPO did not protect DA neurons from 6-hydroxydopamine (6-OHDA) toxicity in a rat model of PD.…”

Section: Introductionmentioning

confidence: 99%

AAV9-mediated erythropoietin gene delivery into the brain protects nigral dopaminergic neurons in a rat model of Parkinson's disease

Zhao

et al. 2009

Gene Ther

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We have recently shown that intrastriatal injection of recombinant human erythropoietin (EPO) protects dopaminergic (DA) neurons in the substantia nigra (SN) from 6-hydroxydopamine (6-OHDA) toxicity in a rat model of Parkinson's disease. However, systemic administration of EPO did not protect nigral DA neurons, suggesting that the blood-brain barrier limits the passage of EPO protein into the brain. In the present study, we used an adenoassociated viral (AAV) serotype 9 (AAV9) vector to deliver the human EPO gene into the brain of 6-OHDA-lesioned rats. We observed that expression of the human EPO gene was robust and stable in the striatum and the SN for up to 10 weeks. EPO-immunoreactive (IR) cells were widespread throughout the injected striatum, and EPO-IR neurons and fibers were also found in the ipsilateral SN. Enzyme-linked immunosorbent assay and western blot analyses exhibited dramatic levels of EPO protein in the injected striatum. As a result, nigral DA neurons were protected against 6-OHDA-induced toxicity. Amphetamine-induced rotational asymmetry and spontaneous forelimb use asymmetry were both attenuated. Interestingly, we also observed that intrastriatal injection of AAV9-EPO vectors led to increased numbers of red blood cells in peripheral blood. This highlights the importance of using an inducible gene delivery system for EPO gene delivery.

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Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production

Cited by 122 publications

References 12 publications

促红细胞生成素对1-甲基-4-苯基吡啶损伤的 Pc12 细胞的保护作用

促红细胞生成素对1-甲基-4-苯基吡啶损伤的 Pc12 细胞的保护作用

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

AAV9-mediated erythropoietin gene delivery into the brain protects nigral dopaminergic neurons in a rat model of Parkinson's disease

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