PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes

Biochem Biophys Res Commun. 2015 Nov 13;467(2):197-203. doi: 10.1016/j.bbrc.2015.10.007. Epub 2015 Oct 8.

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.

Keywords: Astrocytes; NF-kB; PERK; Rat; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Hypoxia
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Gene Expression Regulation
  • Genetic Vectors
  • Glucose / deficiency
  • Glucose / pharmacology*
  • Lentivirus / genetics
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oxygen / pharmacology*
  • Primary Cell Culture
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • eIF-2 Kinase / antagonists & inhibitors
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / metabolism*

Substances

  • NF-kappa B
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • PERK kinase
  • eIF-2 Kinase
  • Glucose
  • Oxygen