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The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats.
J Mol Neurosci. 2017 Mar; 61(3):449-458.JM

Abstract

Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5 % D-galactose for 6 weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7 days. In one group, 2 μl PD98059 was administered 30 min before EPO. Learning and memory ability were analyzed with the Morris water maze system. HE staining was used to observe the morphological changes in the neurons in the hippocampus, and immunohistochemical staining as well as Western blots were carried out to detect the expression of ERK for each group of rats and the expression of phosphorylated-ERK (P-ERK), Nrf2, and superoxide dismutase (SOD). Real-Time PCR was carried out to detect the amount of Nrf2 mRNA and the KEAP1 mRNA expression. EPO can significantly improve learning and memory ability in aging rats and can provide protection against aging by improving the hippocampus morphology. Immunohistochemical staining and Western blots showed P-ERK, Nrf2, and Cu-Zn SOD decreases in aging rats compared to the normal group, while the expression for those proteins increased after EPO intervention. PD98059 inhibited the enhanced expression of P-ERK, Nrf2, and Cu-Zn SOD induced by EPO. Real-Time PCR results suggested that the trend of Nrf2mRNA expression was the same as that for the proteins, which confirmed that the enhancement occurred at the gene level. As such, EPO can significantly resist or delay aging and protect the brain by reducing oxidative stress. The most likely mechanism is that EPO can promote the ERK/Nrf2-ARE pathway in aging rats and that PD98059 can inhibit that process. These findings may facilitate further studies on the mechanism of aging and applications for the neuroprotective properties of EPO for clinical treatments.

Authors+Show Affiliations

Department of Neurology, the Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, People's Republic of China. zjxxpyl@163.com.Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, People's Republic of China.Department of Neurology, the Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, People's Republic of China.Department of Neurology, the Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, People's Republic of China.Department of Neurology, the Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, People's Republic of China.Department of Neurology, the Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, People's Republic of China.Department of Neurology, the Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28168414

Citation

Wu, Haiqin, et al. "The Anti-Aging Effect of Erythropoietin Via the ERK/Nrf2-ARE Pathway in Aging Rats." Journal of Molecular Neuroscience : MN, vol. 61, no. 3, 2017, pp. 449-458.
Wu H, Zhao J, Chen M, et al. The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats. J Mol Neurosci. 2017;61(3):449-458.
Wu, H., Zhao, J., Chen, M., Wang, H., Yao, Q., Fan, J., & Zhang, M. (2017). The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats. Journal of Molecular Neuroscience : MN, 61(3), 449-458. https://doi.org/10.1007/s12031-017-0885-1
Wu H, et al. The Anti-Aging Effect of Erythropoietin Via the ERK/Nrf2-ARE Pathway in Aging Rats. J Mol Neurosci. 2017;61(3):449-458. PubMed PMID: 28168414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats. AU - Wu,Haiqin, AU - Zhao,Jiaxin, AU - Chen,Mengyi, AU - Wang,Huqing, AU - Yao,Qingling, AU - Fan,Jiaxin, AU - Zhang,Meng, Y1 - 2017/02/06/ PY - 2016/09/14/received PY - 2017/01/09/accepted PY - 2017/2/9/pubmed PY - 2017/7/1/medline PY - 2017/2/8/entrez KW - Anti-aging effects KW - Cu-Zn SOD KW - EPO KW - ERK KW - Nrf2 KW - P-ERK SP - 449 EP - 458 JF - Journal of molecular neuroscience : MN JO - J. Mol. Neurosci. VL - 61 IS - 3 N2 - Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5 % D-galactose for 6 weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7 days. In one group, 2 μl PD98059 was administered 30 min before EPO. Learning and memory ability were analyzed with the Morris water maze system. HE staining was used to observe the morphological changes in the neurons in the hippocampus, and immunohistochemical staining as well as Western blots were carried out to detect the expression of ERK for each group of rats and the expression of phosphorylated-ERK (P-ERK), Nrf2, and superoxide dismutase (SOD). Real-Time PCR was carried out to detect the amount of Nrf2 mRNA and the KEAP1 mRNA expression. EPO can significantly improve learning and memory ability in aging rats and can provide protection against aging by improving the hippocampus morphology. Immunohistochemical staining and Western blots showed P-ERK, Nrf2, and Cu-Zn SOD decreases in aging rats compared to the normal group, while the expression for those proteins increased after EPO intervention. PD98059 inhibited the enhanced expression of P-ERK, Nrf2, and Cu-Zn SOD induced by EPO. Real-Time PCR results suggested that the trend of Nrf2mRNA expression was the same as that for the proteins, which confirmed that the enhancement occurred at the gene level. As such, EPO can significantly resist or delay aging and protect the brain by reducing oxidative stress. The most likely mechanism is that EPO can promote the ERK/Nrf2-ARE pathway in aging rats and that PD98059 can inhibit that process. These findings may facilitate further studies on the mechanism of aging and applications for the neuroprotective properties of EPO for clinical treatments. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/28168414/The_Anti_Aging_Effect_of_Erythropoietin_via_the_ERK/Nrf2_ARE_Pathway_in_Aging_Rats_ L2 - https://dx.doi.org/10.1007/s12031-017-0885-1 DB - PRIME DP - Unbound Medicine ER -