Protective effect of suramin against cell death in rat cerebellar granular neurons 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 neuroblastoma cells. Excitotoxicity induced by glutamate was associated with an extensive chromatin condensation, nuclear fragmentation and disintegration of nuclear DNA into the high molecular weight (HMW)-DNA fragments of about 50-100 kb without formation of an oligonucleosomal DNA ladder or caspase activation. Staurosporine-induced cytotoxicity was accompanied by the activation of caspase 3-like protease(s) and disintegration of nuclear DNA into the HMW- and oligonucleosomal DNA fragments. Suramin (100 microM) effectively protected both cultured cerebellar neurons and NB-2a cells against cell death, which appeared as the inhibition of caspase 3-like activity in NB-2a cells, abrogation of both HMW- and internucleosomal DNA fragmentation and maintaining the nuclear morphology indistinguishable of the control cells. Eventually, suramin lead to the marked increase in the cell viability of both cerebellar neurons and NB-2a neuroblastoma cells challenged with glutamate and staurosporine, respectively. We suggest that the novel, neuroprotective activity of suramin may have a therapeutic value in several neuropathological paradigms.
Bezvenyuk
Z
Z
Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Suuronen
T
T
Salminen
A
A
Solovyan
V
V
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology*; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D013498:Suramin; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases