RIP1K Contributes to Neuronal and Astrocytic Cell Death in Ischemic Stroke via Activating Autophagic-lysosomal Pathway

Neuroscience
Yong NiHui-Ling Zhang

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 catheps...Continue Reading

Citations

Jul 6, 2019·Frontiers in Neuroscience·Audrey M ThiebautBenoit D Roussel
Mar 10, 2020·Oxidative Medicine and Cellular Longevity·Danfeng LinAnwen Shao
May 6, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Yi-Yue ZhangJun Peng
May 3, 2019·Proceedings of the National Academy of Sciences of the United States of America·Alexei DegterevJunying Yuan
Feb 25, 2020·Oxidative Medicine and Cellular Longevity·Chunli ChenLiuwang Zeng
Aug 9, 2019·JCI Insight·Mary E ChoiAugustine M K Choi
Oct 18, 2020·Archives of Biochemistry and Biophysics·Suchan LiaoSiriporn C Chattipakorn
Nov 3, 2020·Frontiers in Cellular Neuroscience·Jie LiuYi Yang
Nov 10, 2020·Acta Pharmaceutica Sinica. B·Aqu AluXiawei Wei

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.