Glutamate receptor activation evokes calpain-mediated degradation of Sp3 and Sp4, the prominent Sp-family transcription factors in neurons

Xianrong Mao, Shao Hua Yang, James W. Simpkins, Steven W. Barger

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Sp-family transcription factors (Sp1, Sp3 and Sp4) contain a zinc-finger domain that binds to DNA sequences rich in G-C/T. As assayed by RT-PCR analysis of mRNA, western-blot analysis, immunofluorescence, and antibody-dependent "supershift" of DNA-binding assays, the prominent Sp-family factors in cerebral neurons were identified as Sp3 and Sp4. By contrast, glial cells were found to express Sp1 and Sp3. We previously showed that the pattern of G-C/T binding activity of Sp-family factors is rapidly and specifically altered by the calcium influx accompanying activation of glutamate receptors. Here, we demonstrate that Sp-factor activity is also lost after a cerebral ischemia/reperfusion injury in vivo. Consistent with its calcium-dependent nature, we found that glutamate's effect on Sp-family factors could be blocked by inhibitors of calpains, neutral cysteine proteases activated by calcium. Purified calpain I cleaved Sp3 and Sp4 into products that retained G-C/T-binding activity, consistent with species observed in glutamate-treated neurons. These data provide details of an impact of glutamate-receptor activation on molecular events connected to gene expression.

Original languageEnglish
Pages (from-to)1300-1314
Number of pages15
JournalJournal of Neurochemistry
Volume100
Issue number5
DOIs
StatePublished - Mar 2007

Keywords

  • Astrocyte
  • Calcium
  • Excitotoxicity
  • Ischemia
  • Sp1

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