A New Role Discovered for IGTP: The Protective Effect of IGTP in ICH-Induced Neuronal Apoptosis

Cell Mol Neurobiol. 2016 Jul;36(5):713-24. doi: 10.1007/s10571-015-0251-1. Epub 2015 Aug 5.

Abstract

Interferon gamma-induced GTPase (IGTP), which is also named Irgm3, has been widely described in regulating host resistance against intracellular pathogens. Previous researches have demonstrated that IGTP exerts beneficial function during coxsackievirus B3 (CVB3) infection. However, little information is available regarding the role of IGTP in central nervous system. Here, our study revealed that IGTP may have an essential role during ICH-induced neuronal apoptosis. We found the expression level of IGTP adjacent to hematoma was strongly increased after ICH, accompanied with the up-regulation of proliferating cell nuclear antigen (PCNA), active-caspase-3, p-GSK-3β, and Bax. IGTP was also observed to be co-localized with PCNA in astrocytes and active-caspase-3 in neurons, indicating its association with astrocyte proliferation and neuronal apoptosis after ICH. Finally, in vitro study, knocking down IGTP with IGTP-specific siRNA promoted active-caspase-3, p-GSK-3β, and Bax expression, and led to more severe neuronal apoptosis after ICH. All these results above suggested that IGTP might play a critical role in protecting neurons from apoptosis after ICH.

Keywords: Apoptosis; IGTP; Intracerebral hemorrhage; Proliferation; Rat.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Astrocytes / cytology
  • Astrocytes / enzymology*
  • Caspase 3 / metabolism
  • Cerebral Hemorrhage / metabolism*
  • Disease Models, Animal
  • GTP Phosphohydrolases / metabolism*
  • Neurons / cytology
  • Neurons / enzymology*
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation

Substances

  • Casp3 protein, rat
  • Caspase 3
  • GTP Phosphohydrolases
  • igtp protein, rat