Methylation of cortical brain proteins from patients with HIV infection.
OBJECTIVE
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.


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-adenosylmethionine) 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. Carboxymethyltransferase 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.


CONCLUSIONS
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.
Goggins
M
M
Department of Clinical Medicine, Trinity College, Dublin, Ireland.
Scott
J M
JM
Weir
D G
DG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology*; D018792:Encephalitis, Viral / Q000503:physiopathology*; D015658:HIV Infections / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011496:Protein Methyltransferases / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D011496:Protein Methyltransferases