Suppression of PrP^Sc- and HIV-1 gp120 induced neuronal cell death by sulfated colominic acid

Abstract

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 50.3 mg/ml when preincubated with the neurons or PrP Sc . Rat cortical cells also undergo apoptosis after incubation with the HIV-1 coat protein gp120 in vitro. This effect was abolished also by sulfated colominic acid when preincubated with the cells or gp120. Addition of 0.3 mg/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 gp120 alone (containing about 40% viable cells). Sulfated colominic acid does not act as antagonist of NMDA receptor channels at concentrations of up to 3 mg/ml when co-administered with 100 mg/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 mg/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.

Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: Cell density-dependent effects prevented by sulfation

“…O-sulfated CA (SCA), prepared by the chemical sulfation of CA (Mulligan et al, 1998), has several biological activities, including antiviral activities (Young et al, 1996;Ushijima et al, 1999;Konishi et al, 2000), inhibition of the cytotoxic action of bee and snake venom (Oda et al, 1999), inhibition of P-selectin-dependent macrophage infiltration in the glomeruli in experimental crescentic glomerulonephritis in rats (Ogawa et al, 2002), and inhibition of the fertilization of mouse gametes (Kawai et al, 2000). Recently, we have shown that both CA and SCA inhibit the proliferation of cultured vascular smooth muscle cells without nonspecific cell damage .…”

Rapid hematopoietic progenitor mobilization by sulfated colominic acid

“…It has been reported that sulfated colominic acid (SCA, structure is shown in supplemental Fig. 1S) exhibits anti-HIV activity [12], and suppresses scrapie prion protein (PrP Sc ) and HIV-1 gp-120-induced neuronal cell death [13]. Since recent accumulating evidences suggest that CXCR4 and CD26 play critical roles in HIV entry as co-receptors [14,15], it is possible that SCA modulates CXCR4 and/or CD26.…”

The Biological Effects of Depolymerized Sodium Spirulan and Sulfated Colominic Acid on Vascular Cells are Beneficial in Preventing Atherosclerosis

“…1B), originally isolated from Escherichia coli K1. 21) Although little is known about the biological activity of CA, O-sulfated CA (SCA), prepared by chemical sulfation of the CA chain, 22) exhibits several biological activities, including antiviral activities, [23][24][25] inhibition of the cytotoxic action of bee and snake venom, 26) inhibition of Pselectin-dependent macrophage infiltration in the glomeruli in experimental rats with crescentic glomerulonephritis, 27) and inhibition of the fertilization of mouse gametes. 28) However, the effects of CA and SCA on the vascular cell functions as well as the blood coagulation-fibrinolytic system have not been investigated.…”