Elevated N1-acetylspermidine levels in gerbil and rat brains after CNS injury

A. Muralikrishna Rao, James F. Hatcher, Aclan Doǧan, Robert J. Dempsey

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The polyamine system is very sensitive to different pathological states of the brain and is perturbed after CNS injury. The main modifications are significant increases in ornithine decarboxylase activity and an increase in tissue putrescine levels. Previously we have shown that the specific polyamine oxidase (PAO) inhibitor N1,N4-bis(2,3-butadienyl)-1,4- butanediamine (MDL 72527) reduced the tissue putrescine levels, edema, and infarct volume after transient focal cerebral ischemia in spontaneously hypertensive rats and traumatic brain injury of Sprague-Dawley rats. In the present study, N1-acetylspermidine accumulation was greater in injured brain regions compared with sham or contralateral regions following inhibition of PAO by MDL 72527. This indicates spermidine/spermine-N1-acetyltransferase (SSAT) activation after CNS injury. The observed increase in N1- acetylspermidine levels at 1 day after CNS trauma paralleled the decrease in putrescine levels after treatment with MDL 72527. This suggests that the increased putrescine formation at 1 day after CNS injury is mediated by the SSAT/PAO pathway, consistent with increased SSAT mRNA after transient ischemia.

Original languageEnglish (US)
Pages (from-to)1106-1111
Number of pages6
JournalJournal of neurochemistry
Volume74
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Cerebral ischemia
  • MDL 72527
  • Omithine decarboxylase
  • Polyamine interconversion pathway
  • Polyamine oxidase
  • Polyamines
  • Putrescine
  • Spermidine/spermine-N-acetyltransferase
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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