Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1

Cell Mol Neurobiol. 2015 Nov;35(8):1073-9. doi: 10.1007/s10571-015-0215-5. Epub 2015 Jul 2.

Abstract

Scorpion venom has been used in the Orient to treat central nervous system diseases for many years, and the protein/peptide toxins in Buthus martensii Karsch (BmK) venom are believed to be the effective components. Scorpion venom heat-resistant peptide (SVHRP) is an active component of the scorpion venom extracted from BmK. In a previous study, we found that SVHRP could inhibit the formation of a glial scar, which is characterized by enhanced glial fibrillary acidic protein (GFAP) expression, in the epileptic hippocampus. However, the cellular and molecular mechanisms underlying this process remain to be clarified. The results of the present study indicate that endogenous GFAP expression in primary rat astrocytes was attenuated by SVHRP. We further demonstrate that the suppression of GFAP was primarily mediated by inhibiting both c-Jun expression and its binding with AP-1 DNA binding site and other factors at the GFAP promoter. These results support that SVHRP contributes to reducing GFAP at least in part by decreasing the activity of the transcription factor AP-1. In conclusion, the effects of SVHRP on astrocytes with respect to the c-Jun/AP-1 signaling pathway in vitro provide a practical basis for studying astrocyte activation and inhibition and a scientific basis for further studies of traditional medicine.

Keywords: Astrocyte; Glial fibrillary acidic protein (GFAP); Scorpion venom heat-resistant peptide (SVHRP); c-Jun.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / antagonists & inhibitors
  • Glial Fibrillary Acidic Protein / biosynthesis*
  • Hot Temperature
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / biosynthesis*
  • Peptides / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Scorpion Venoms / toxicity*
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Transcription Factor AP-1 / biosynthesis*

Substances

  • Glial Fibrillary Acidic Protein
  • Peptides
  • Scorpion Venoms
  • Transcription Factor AP-1
  • scorpion venom heat-resistant peptide, Buthus martensii
  • JNK Mitogen-Activated Protein Kinases