title: PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes.
abstract: Mitochondrial dysfunction is a direct target of hypoxic/ischemic stress in astrocytes, which results in the increased production of reactive oxygen species (ROS). Previous reports showed that ROS can activate NF-kB in spinal cord astrocytes, which occurs as a secondary injury during the pathological process of spinal cord injury (SCI). Protein kinase RNA (PKR)-like ER kinase (PERK) plays an important role in mitochondrial dysfunction. To elucidate the specific role of PERK in hypoxic/ischemic-induced NF-kB activation in spinal astrocytes, we utilized an in vitro oxygen-glucose deprivation (OGD) model, which showed an enhanced formation of ROS and NF-kB activation. Knockdown of PERK resulted in reduced activation of PERK and ROS generation in astrocytes under OGD conditions. Notably, the knockdown of PERK also induced NF-kB activation in astrocytes. These data suggest that PERK is required for the hypoxic/ischemic-induced-dependent regulation of ROS and that it is involved in NF-kB activation in the astrocytes.
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, Jiangsu, China. Electronic address: ljb_cz@163.com.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Du
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005947:Glucose; D016328:NF-kappa B; D010100:Oxygen; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D019892:eIF-2 Kinase
keywords: Astrocytes; NF-kB; PERK; Rat; Spinal cord injury