Expression of Sam68 Associates with Neuronal Apoptosis and Reactive Astrocytes After Spinal Cord Injury

Cell Mol Neurobiol. 2017 Apr;37(3):487-498. doi: 10.1007/s10571-016-0384-x. Epub 2016 May 28.

Abstract

Src-associated in mitosis (Sam68; 68 kDa) is a novel RNA-binding protein that belongs to the signal transduction and activation of RNA family involved in various biological processes. However, the expression and roles of Sam68 in the central nervous system remain unknown. In the present study, we performed a spinal cord injury (SCI) model in adult rats and found a significant increase of Sam68 protein levels in this model, which reached a peak at day 3 and then gradually returned to normal levels at day 14 after SCI. We use immunohistochemistry analysis revealing a widespread distribution of Sam68 in the spinal cord. In addition, double-immunofluorescence staining showed that Sam68 immunoreactivity was found predominantly in neurons and astrocytes. Moreover, colocalization of Sam68/active caspase-3 has been respectively detected in neuronal nuclei, and colocalization of Sam68/PCNA has been detected in glial fibrillary acidic protein. In vitro, we found that depletion of Sam68 by short interfering RNA inhibits neuronal apoptosis and astrocyte proliferation and decreases cyclin D1 protein levels. In conclusion, this is the first study to find the Sam68 expression in SCI. Our results suggest that Sam68 might be illustrated in the apoptosis of neurons and proliferation of astrocytes after SCI. This research will provide new drug targets for clinical treatment of SCI.

Keywords: Cell cycle; Neuronal apoptosis; Proliferation; Rat; Sam68; Spinal cord injury.

MeSH terms

  • Animals
  • Apoptosis*
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Biomarkers / metabolism
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Proliferation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Hindlimb / pathology
  • Hindlimb / physiopathology
  • Immunohistochemistry
  • Male
  • Motor Activity
  • Neurons / metabolism*
  • Neurons / pathology*
  • Phenotype
  • RNA, Small Interfering / metabolism
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Khdrbs1 protein, rat
  • RNA, Small Interfering