Protective effect of suramin against cell death in rat cerebellar granularneurons and mouse neuroblastoma cells

In this report, we examined the effect of suramin on the cell death induced by glutamate in cerebellar granule neurons or by staurosporine in NB-2a ne uroblastoma cells. Excitotoxicity induced by glutamate was associated with an extensive chromatin condensation, nuclear fragmentation and disintegrati on of nuclear DNA into the high molecular weight (HMW)-DNA fragments of abo ut 50-100 kb without formation of an oligonucleosomal DNA ladder or caspase activation. Staurosporine-induced cytotoxicity was accompanied by the acti vation of caspase 3-like protease(s) and disintegration of nuclear DMA into the HMW- and oligonucleosomal DNA fragments. Suramin (100 mu M) effectivel y protected both cultured cerebellar neurons and NB-2a cells against cell d eath, which appeared as the inhibition of caspase 3-like activity in NB-2a cells, abrogation of both HMW- and internucleosomal DNA fragmentation and m aintaining the nuclear morphology indistinguishable of the control cells. E ventually, suramin lead to the marked increase in the cell viability of bot h cerebellar neurons and NB-2a neuroblastoma cells challenged with glutamat e and staurosporine, respectively. We suggest that the novel, neuroprotecti ve activity of suramin may have a therapeutic value in several neuropatholo gical paradigms. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved .