Methylation of cortical brain proteins from patients with HIV infection

Michael Goggins, J. M. Scott, D. G. Weir

Research output: Contribution to journalArticle

Abstract

Objectives - Experimental models of vitamin B12 deficient-neuropathy are characterized by central nervous system protein hypomethylation. The encephalitis/vacuolar myelopathy complicating HIV infection and subacute combined degeneration of the cord due to vitamin B12 deficiency share similar biochemical and pathological abnormalities. Altered central nervous system methylation may be important in the pathogenesis of HIV encephalitis. To test this hypothesis we compared brain protein methylation of HIV- positive, and control, subjects. Materials and methods - Carboxymethyltransferase activity was assayed in postmortem cortical brain samples obtained from 16 control patients (9 males); mean age (59±5.1 years, range 21-87 years), 9 HIV-positive patients (7 males, 6 IVDA, 3 homosexual, 4 with HIV encephalitis, mean age 37, range 23-45), and 3 patients with Alzheimer's disease (mean age 78 years). Results - The amount of radiolabelled SAM (S-adenosyl-methionine) incorporated into carboxymethyl, and N-methylation sites within brain proteins from cortical white matter in vitro was significantly lower (P<0.05) in the HIV+ group vs controls. Carboxymethyl- transferase activity was similar in the HIV- infected brains irrespective of the presence or absence of HIV encephalitis. Mean cortical methyl group incorporation was also lower in the Alzheimer's disease group compared to controls. Conclusion - The observation of reduced in vitro methylation of brain proteins from patients with HIV infection and Alzheimer's disease suggests that fewer unmethylated sites exist due to relative protein hypermethylation in vivo. The absence of hypomethylation in the brains of patients with HIV encephalitis suggests that hypomethylation is not necessary for the development of HIV encephalitis.

Original languageEnglish (US)
Pages (from-to)326-331
Number of pages6
JournalActa Neurologica Scandinavica
Volume100
Issue number5
StatePublished - Oct 25 1999

Keywords

  • Alzheimer's disease
  • HIA encephalitis
  • Protein carboxmethyltransferase
  • Protein methylation
  • S-adenosylhomocysteine
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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