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RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke via Activating Autophagic-lysosomal Pathway.
Neuroscience. 2018 02 10; 371:60-74.N

Abstract

Although the receptor-interacting protein 1 kinase (RIP1K)-regulated necroptosis can be evoked by cerebral ischemia, the effects of RIP1K in mediating neuronal and astrocytic cell death and the underlying mechanisms remain poorly understood. This study evaluates the contribution of RIP1K to ischemic stroke-induced neuronal and astrocytic cell death, and the activation of autophagic-lysosomal pathway. Using an in vitro oxygen and glucose deprivation (OGD) in primary cultured neurons or astrocytes and a permanent middle cerebral artery occlusion (pMCAO) model in rats or mice, we observed the role of RIP1K in the ischemic neuronal and astrocytic cell death and the underlying mechanisms by pharmacological or genetic inhibition of RIP1K. pMCAO or OGD condition led to an increase in RIP1K, RIP3K and RIP1K-RIP3K complex. RIP1K knockdown or necrostatin-1 (Nec-1, a specific inhibitor of RIP1K) treatment reduced infarct volume, improved neurological deficits, increased microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) levels, and attenuated neuronal or astrocytic necrotic cell death in the ischemic cortex. RIP1K knockdown decreased RIP1K-RIP3K complex formation, light chain 3 II (LC3II) and active cathepsin B levels and lysosomal membrane permeability (LMP). Furthermore, a combination of Nec-1 and an inhibitor of autophagy or cathepsin B produced an enhancement of protective effect on neuronal or astrocytic cell death. RIP1K-mediated necroptosis may play important roles in ischemia-induced neuronal and astrocytic cell death through the activation of autophagic-lysosomal pathway.

Authors+Show Affiliations

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.Guangzhou Institute of Traumatic surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China.Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.Stroke Outcomes Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX; and Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston 77030, TX, United States.Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.Department of Anesthesiology and Perioperative Medicine, Suzhou Science and Technology Town Hospital; and Institute of Clinical Medicine, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215153, PR China.Stroke Outcomes Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX; and Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston 77030, TX, United States.Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China. Electronic address: zhanghuiling@suda.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

29102662

Citation

Ni, Yong, et al. "RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke Via Activating Autophagic-lysosomal Pathway." Neuroscience, vol. 371, 2018, pp. 60-74.
Ni Y, Gu WW, Liu ZH, et al. RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke via Activating Autophagic-lysosomal Pathway. Neuroscience. 2018;371:60-74.
Ni, Y., Gu, W. W., Liu, Z. H., Zhu, Y. M., Rong, J. G., Kent, T. A., Li, M., Qiao, S. G., An, J. Z., & Zhang, H. L. (2018). RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke via Activating Autophagic-lysosomal Pathway. Neuroscience, 371, 60-74. https://doi.org/10.1016/j.neuroscience.2017.10.038
Ni Y, et al. RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke Via Activating Autophagic-lysosomal Pathway. Neuroscience. 2018 02 10;371:60-74. PubMed PMID: 29102662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke via Activating Autophagic-lysosomal Pathway. AU - Ni,Yong, AU - Gu,Wei-Wei, AU - Liu,Zhi-He, AU - Zhu,Yong-Ming, AU - Rong,Jia-Guo, AU - Kent,Thomas A, AU - Li,Min, AU - Qiao,Shi-Gang, AU - An,Jian-Zhong, AU - Zhang,Hui-Ling, Y1 - 2017/11/08/ PY - 2016/11/29/received PY - 2017/10/20/revised PY - 2017/10/24/accepted PY - 2017/11/6/pubmed PY - 2018/12/12/medline PY - 2017/11/6/entrez KW - ISCHEMIC stroke KW - RIP1K KW - astrocyte KW - autophagic-lysosomal pathway KW - neuron KW - neuroprotection SP - 60 EP - 74 JF - Neuroscience JO - Neuroscience VL - 371 N2 - Although the receptor-interacting protein 1 kinase (RIP1K)-regulated necroptosis can be evoked by cerebral ischemia, the effects of RIP1K in mediating neuronal and astrocytic cell death and the underlying mechanisms remain poorly understood. This study evaluates the contribution of RIP1K to ischemic stroke-induced neuronal and astrocytic cell death, and the activation of autophagic-lysosomal pathway. Using an in vitro oxygen and glucose deprivation (OGD) in primary cultured neurons or astrocytes and a permanent middle cerebral artery occlusion (pMCAO) model in rats or mice, we observed the role of RIP1K in the ischemic neuronal and astrocytic cell death and the underlying mechanisms by pharmacological or genetic inhibition of RIP1K. pMCAO or OGD condition led to an increase in RIP1K, RIP3K and RIP1K-RIP3K complex. RIP1K knockdown or necrostatin-1 (Nec-1, a specific inhibitor of RIP1K) treatment reduced infarct volume, improved neurological deficits, increased microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) levels, and attenuated neuronal or astrocytic necrotic cell death in the ischemic cortex. RIP1K knockdown decreased RIP1K-RIP3K complex formation, light chain 3 II (LC3II) and active cathepsin B levels and lysosomal membrane permeability (LMP). Furthermore, a combination of Nec-1 and an inhibitor of autophagy or cathepsin B produced an enhancement of protective effect on neuronal or astrocytic cell death. RIP1K-mediated necroptosis may play important roles in ischemia-induced neuronal and astrocytic cell death through the activation of autophagic-lysosomal pathway. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/29102662/RIP1K_Contributes_to_Neuronal_and_Astrocytic_Cell_Death_in_Ischemic_Stroke_via_Activating_Autophagic_lysosomal_Pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(17)30766-2 DB - PRIME DP - Unbound Medicine ER -