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CKIP-1 alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in cultured hippocampal neurons by downregulating Keap1 and activating Nrf2/ARE signaling.
Eur J Pharmacol. 2019 Apr 05; 848:140-149.EJ

Abstract

Accumulating evidence has shown that casein kinase 2 interacting protein-1 (CKIP-1) is a pivotal regulator of apoptosis and oxidative stress. However, whether CKIP-1 is involved in regulating neuronal injury during the progression of cerebral ischemia/reperfusion injury remains unknown. In the present study, we aimed to investigate the potential role and underlying mechanism of CKIP-1 in regulating neuronal apoptosis and oxidative stress induced by oxygen-glucose deprivation/reoxygenation (OGD/R) treatment in vitro. Herein, we found that OGD/R treatment resulted in a significant increase in CKIP-1 expression in cultured hippocampal neurons. The silencing of CKIP-1 exacerbated OGD/R-induced neuronal apoptosis and production of reactive oxygen species. By contrast, CKIP-1 overexpression reduced the apoptosis and reactive oxygen species production induced by the OGD/R treatment. Mechanistically, CKIP-1 inhibited the expression of Kelch-like ECH-associated protein 1 (Keap1) and promoted the expression of nuclear factor E2-related factor 2 (Nrf2). In addition, CKIP-1 increased the activation of antioxidant response element and the expression of downstream antioxidant genes. However, Keap1 overexpression or Nrf2 knockdown partially reversed the neuroprotective effect of CKIP-1 overexpression. Taken together, our results demonstrate that CKIP-1 overexpression alleviates OGD/R-induced neuronal injury by enhancing the Nrf2-mediated anti-oxidative stress signaling pathway, revealing a neuroprotective role of CKIP-1. Our study suggests CKIP-1 as a potential therapeutic target for neuroprotection.

Authors+Show Affiliations

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Neurosurgery, Xianyang Central Hospital, Xianyang 712000, China.Department of Neurosurgery, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, China.Department of Ophthalmology, The First People's Hospital of Xianyang City, Xianyang 712000, China.Pain Clinic, Xi'an Central Hospital, Xi'an 710003, China.Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: guo_shiwensw@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30658115

Citation

Xiang, Yi, et al. "CKIP-1 Alleviates Oxygen-glucose Deprivation/reoxygenation-induced Apoptosis and Oxidative Stress in Cultured Hippocampal Neurons By Downregulating Keap1 and Activating Nrf2/ARE Signaling." European Journal of Pharmacology, vol. 848, 2019, pp. 140-149.
Xiang Y, Fan X, Zhao M, et al. CKIP-1 alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in cultured hippocampal neurons by downregulating Keap1 and activating Nrf2/ARE signaling. Eur J Pharmacol. 2019;848:140-149.
Xiang, Y., Fan, X., Zhao, M., Guo, Q., & Guo, S. (2019). CKIP-1 alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in cultured hippocampal neurons by downregulating Keap1 and activating Nrf2/ARE signaling. European Journal of Pharmacology, 848, 140-149. https://doi.org/10.1016/j.ejphar.2019.01.015
Xiang Y, et al. CKIP-1 Alleviates Oxygen-glucose Deprivation/reoxygenation-induced Apoptosis and Oxidative Stress in Cultured Hippocampal Neurons By Downregulating Keap1 and Activating Nrf2/ARE Signaling. Eur J Pharmacol. 2019 Apr 5;848:140-149. PubMed PMID: 30658115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CKIP-1 alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in cultured hippocampal neurons by downregulating Keap1 and activating Nrf2/ARE signaling. AU - Xiang,Yi, AU - Fan,Xiaoxuan, AU - Zhao,Ming, AU - Guo,Qiang, AU - Guo,Shiwen, Y1 - 2019/01/15/ PY - 2018/11/27/received PY - 2019/01/11/revised PY - 2019/01/14/accepted PY - 2019/1/19/pubmed PY - 2019/6/7/medline PY - 2019/1/19/entrez KW - CKIP-1 KW - Keap1 KW - Nrf2 KW - Oxygen-glucose deprivation/reoxygenation SP - 140 EP - 149 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 848 N2 - Accumulating evidence has shown that casein kinase 2 interacting protein-1 (CKIP-1) is a pivotal regulator of apoptosis and oxidative stress. However, whether CKIP-1 is involved in regulating neuronal injury during the progression of cerebral ischemia/reperfusion injury remains unknown. In the present study, we aimed to investigate the potential role and underlying mechanism of CKIP-1 in regulating neuronal apoptosis and oxidative stress induced by oxygen-glucose deprivation/reoxygenation (OGD/R) treatment in vitro. Herein, we found that OGD/R treatment resulted in a significant increase in CKIP-1 expression in cultured hippocampal neurons. The silencing of CKIP-1 exacerbated OGD/R-induced neuronal apoptosis and production of reactive oxygen species. By contrast, CKIP-1 overexpression reduced the apoptosis and reactive oxygen species production induced by the OGD/R treatment. Mechanistically, CKIP-1 inhibited the expression of Kelch-like ECH-associated protein 1 (Keap1) and promoted the expression of nuclear factor E2-related factor 2 (Nrf2). In addition, CKIP-1 increased the activation of antioxidant response element and the expression of downstream antioxidant genes. However, Keap1 overexpression or Nrf2 knockdown partially reversed the neuroprotective effect of CKIP-1 overexpression. Taken together, our results demonstrate that CKIP-1 overexpression alleviates OGD/R-induced neuronal injury by enhancing the Nrf2-mediated anti-oxidative stress signaling pathway, revealing a neuroprotective role of CKIP-1. Our study suggests CKIP-1 as a potential therapeutic target for neuroprotection. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/30658115/CKIP_1_alleviates_oxygen_glucose_deprivation/reoxygenation_induced_apoptosis_and_oxidative_stress_in_cultured_hippocampal_neurons_by_downregulating_Keap1_and_activating_Nrf2/ARE_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(19)30023-8 DB - PRIME DP - Unbound Medicine ER -