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Antioxidant effect of erythropoietin on 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells.
Eur J Pharmacol. 2007 Jun 14; 564(1-3):47-56.EJ

Abstract

The neuroprotective effects of erythropoietin on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress and apoptosis in cultured PC12 cells as well as the underlying mechanism were investigated. Treatment of PC12 cells with MPP(+) caused the loss of cell viability, which was associated with the elevation in apoptotic rate, the formation of reactive oxygen species and the disruption of mitochondrial transmembrane potential. It was also shown that MPP(+) significantly induced upregulation of Bax/Bcl-2 ratio and activation of caspase-3. In contrast, erythropoietin reversed these phenotypes and had its maximum protective effect at 1 U/ml. The effect of erythropoietin was mediated by the phosphatidylinositol 3-kinase (PI3K) signaling pathway since erythropoietin failed to rescue cells from MPP(+) insult in the presence of the PI3K inhibitor, LY 294002. In addition, the downstream effector of PI3K, Akt, was activated by erythropoietin, and Akt activation was inhibited by LY 294002. Furthermore, the effect of erythropoietin on reactive oxygen species levels was also blocked by LY 294002. These results show that erythropoietin may provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative diseases such as Parkinson disease.

Authors+Show Affiliations

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17362920

Citation

Wu, Yan, et al. "Antioxidant Effect of Erythropoietin On 1-methyl-4-phenylpyridinium-induced Neurotoxicity in PC12 Cells." European Journal of Pharmacology, vol. 564, no. 1-3, 2007, pp. 47-56.
Wu Y, Shang Y, Sun S, et al. Antioxidant effect of erythropoietin on 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells. Eur J Pharmacol. 2007;564(1-3):47-56.
Wu, Y., Shang, Y., Sun, S., & Liu, R. (2007). Antioxidant effect of erythropoietin on 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells. European Journal of Pharmacology, 564(1-3), 47-56.
Wu Y, et al. Antioxidant Effect of Erythropoietin On 1-methyl-4-phenylpyridinium-induced Neurotoxicity in PC12 Cells. Eur J Pharmacol. 2007 Jun 14;564(1-3):47-56. PubMed PMID: 17362920.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antioxidant effect of erythropoietin on 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells. AU - Wu,Yan, AU - Shang,You, AU - Sun,Shenggang, AU - Liu,Rengang, Y1 - 2007/02/17/ PY - 2006/10/25/received PY - 2007/01/20/revised PY - 2007/02/02/accepted PY - 2007/3/17/pubmed PY - 2007/8/19/medline PY - 2007/3/17/entrez SP - 47 EP - 56 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 564 IS - 1-3 N2 - The neuroprotective effects of erythropoietin on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress and apoptosis in cultured PC12 cells as well as the underlying mechanism were investigated. Treatment of PC12 cells with MPP(+) caused the loss of cell viability, which was associated with the elevation in apoptotic rate, the formation of reactive oxygen species and the disruption of mitochondrial transmembrane potential. It was also shown that MPP(+) significantly induced upregulation of Bax/Bcl-2 ratio and activation of caspase-3. In contrast, erythropoietin reversed these phenotypes and had its maximum protective effect at 1 U/ml. The effect of erythropoietin was mediated by the phosphatidylinositol 3-kinase (PI3K) signaling pathway since erythropoietin failed to rescue cells from MPP(+) insult in the presence of the PI3K inhibitor, LY 294002. In addition, the downstream effector of PI3K, Akt, was activated by erythropoietin, and Akt activation was inhibited by LY 294002. Furthermore, the effect of erythropoietin on reactive oxygen species levels was also blocked by LY 294002. These results show that erythropoietin may provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative diseases such as Parkinson disease. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17362920/Antioxidant_effect_of_erythropoietin_on_1_methyl_4_phenylpyridinium_induced_neurotoxicity_in_PC12_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00182-3 DB - PRIME DP - Unbound Medicine ER -