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

被引:32
作者
Wu Y. [1 ]
Shang Y. [2 ]
Sun S.-G. [1 ]
Liu R.-G. [3 ]
Yang W.-Q. [4 ]
机构
[1] Department of Neurology, Union Hospital, Huazhong University of Science and Technology
[2] Department of Anesthesiology, Union Hospital, Huazhong University of Science and Technology
[3] Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology
[4] Department of Neurology, Dongfeng Hospital, Yunyang Medical College
基金
中国国家自然科学基金;
关键词
1-methyl-4-phenylpyridinium; Apoptosis; Erythropoietin; Oxidative stress; PC12; cells;
D O I
10.1007/s12264-007-0023-0
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:156 / 164
页数:8
相关论文
共 38 条
  • [1] Lotharius J., O'Malley K.L., The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. A novel mechanism of toxicity, J Biol Chem, 275, pp. 38581-38588, (2000)
  • [2] Itano Y., Kitamura Y., Nomura Y., 1-Methyl-4-phenylpyridinium (MPP <sup>+</sup>)-induced cell death in PC12 cells: Inhibitory effects of several drugs, Neurochem Int, 25, pp. 419-424, (1994)
  • [3] Alam Z.I., Jenner A., Daniel S.E., Lees A.J., Cairns N., Marsden C.D., Et al., Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra, J Neurochem, 69, pp. 1196-1203, (1997)
  • [4] Li Y., Takemura G., Okada H., Miyata S., Maruyama R., Li L., Et al., Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure, Cardiovasc Res, 71, pp. 684-694, (2006)
  • [5] Nakamura T., Sugaya T., Kawagoe Y., Suzuki T., Ueda Y., Koide H., Effect of erythropoietin on urinary liver-type fatty-acid-binding protein in patients with chronic renal failure and anemia, Am J Nephrol, 26, pp. 276-280, (2006)
  • [6] Kumral A., Tugyan K., Gonenc S., Genc K., Genc S., Sonmez U., Et al., Protective effects of erythropoietin against ethanol-induced apoptotic neurodegenaration and oxidative stress in the developing C57BL/6 mouse brain, Dev Brain Res, 160, pp. 146-156, (2005)
  • [7] Ehrenreich H., Aust C., Krampe H., Jahn H., Jacob S., Herrmann M., Et al., Erythropoietin: Novel approaches to neuroprotection in human brain disease, Metab Brain Dis, 19, pp. 195-206, (2004)
  • [8] Knabe W., Knerlich F., Washausen S., Kietzmann T., Siren A.L., Brunnett G., Et al., Ehrenreich H. Expression patterns of erythropoietin and its receptor in the developing midbrain, Anat Embryol, 207, pp. 503-512, (2004)
  • [9] Signore A.P., Weng Z., Hastings T., Van Laar A.D., Liang Q., Lee Y.J., Et al., Erythropoietin protects against 6-hydroxydopamine-induced dopaminergic cell death, J Neurochem, 96, pp. 428-443, (2006)
  • [10] Marti H.H., Wenger R.H., Rivas L.A., Straumann U., Digicaylioglu M., Henn V., Et al., Erythropoietin gene expression in human monkey and murine brain, Eur J Neurosci, 8, pp. 666-676, (1996)