GART expression in rat spinal cord after injury and its role in inflammation

Brain Res. 2014 May 20;1564:41-51. doi: 10.1016/j.brainres.2014.03.044. Epub 2014 Apr 4.

Abstract

The glycinamide ribonucleotide transformylase (GART) gene, a trifunctional polypeptide, has phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, and phosphoribosylaminoimidazole synthetase activity, and is required for de novo purine biosynthesis. GART is highly conserved in vertebrates. Alternative splicing of GART results in two transcript variants encoding different isoforms. However, the expression and function of GART in the central nervous system lesion are still unclear. In this study, we used a traumatic spinal cord injury (SCI) model in adult Sprague-Dawley rats and investigated the dynamic changes of GART protein expression in the spinal cord. Western blot analysis revealed that GART was present in sham-operated spinal cord. It gradually increased, reached a peak at day 3 after SCI, and then declined during the following days. Double immunofluorescence staining revealed a widespread of GART, and the majority of GARTs are detected in astrocytes. After injury, GART expression was increased predominantly in astrocytes, positively correlated with the highly expressed proliferating cell nuclear antigen (PCNA). Knockdown of GART expression in cultured primary astrocytes by siRNA revealed that expression of GART in astrocytes plays a role in the LPS-induced release of pro-inflammatory factors, such as TNF-α and IL-6. These results showed that GART may participate in the pathophysiology of SCI, and more research is needed to have a good understanding of its function and mechanism.

Keywords: GART; Inflammatory; Rats; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / enzymology
  • Astrocytes / metabolism
  • Cytokines / metabolism
  • Inflammation / enzymology
  • Male
  • Motor Activity
  • Phosphoribosylglycinamide Formyltransferase / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / enzymology*
  • Spinal Cord Injuries / metabolism

Substances

  • Cytokines
  • Phosphoribosylglycinamide Formyltransferase