Suppression of PrP(Sc)- and HIV-1 gp120 induced neuronal cell death by sulfated colominic acid.
The scrapie prion protein (PrP(Sc)) has been shown to induce apoptosis of rat cortical neurons in vitro. Here we demonstrate that the toxic effect displayed by PrP(Sc) can be blocked by sulfated colominic acid (polymer of N-acetylneuraminic acid). This compound acts neuroprotectively at a concentration of > or = 0.3 microg/ml when preincubated with the neurons or PrP(Sc). Rat cortical cells also undergo apoptosis after incubation with the HIV-1 coat protein gpl20 in vitro. This effect was abolished also by sulfated colominic acid when preincubated with the cells or gpl20. Addition of 0.3 microg/ml of compound resulted in an increase in cell viability by about 1.6-1.9-fold compared to cultures incubated for 18 h with 30 ng/ml of PrP(Sc) or 20 ng/ml of gpl20 alone (containing about 40% viable cells). Sulfated colominic acid does not act as antagonist of NMDA receptor channels at concentrations of up to 3 microg/ml when co-administered with 100 microg/ml of NMDA. It displayed a strong cytoprotective effect on human T lymphoblastoid CEM cells exposed to HIV-1; a 50% protection occurred after preincubation of the cells with 0.43 microg/ml of compound. At the same concentration, the compound caused an inhibition of HIV-1-induced syncytium formation. Sulfated colominic acid may be a promising compound for treatment of dementia caused by PrP(Sc) and HIV-1 infections.
Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Japan.
H
H
Ushijima
S
S
Perovic
J
J
Leuck
P G
PG
Rytik
W E
WE
Müller
H C
HC
Schröder
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain; D002478:Cells, Cultured; D006224:Cricetinae; D015699:HIV Envelope Protein gp120 / Q000187:drug effects*; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology*; D013997:Time Factors
D015699:HIV Envelope Protein gp120; D018696:Neuroprotective Agents; D011134:Polysaccharides; D018620:PrPSc Proteins; D013431:Sulfates; D016202:N-Methylaspartate