The semisynthetic glycosphingolipid LIGA20 potently protects neurons against apoptosis.
LIGA20 (a semisynthetic GM1 with n-dichloroacetyl sphingosine) having antinecrotic properties was evaluated as an antiapoptotic agent using cerebellar granule cells as a neuronal model. Neurons exposed to medium containing 5 mM K+ in absence of serum (apoptotic medium) for up to 22 h resulted in 65% cell death, accompanied by oligonucleosomal laddering, and a 15-fold-increase in caspase-3 activity. The relationships between times required for enzyme activation and cell death suggests a linkage between these two events. Pretreatment with 10 microM LIGA20 for 10 min significantly attenuated the aforementioned apoptotic changes. LIGA20 also attenuated apoptosis induced by Pb2+, ethanol, and C6-ceramide. Data show that LIGA20 is a versatile neuroprotective agent protecting cells from multiple pathways of cell death.
Nathan S. Kline Institute of Psychiatric Research, Center for Neurochemistry, Orangeburg, New York 10962, USA.
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053938:DNA Fragmentation; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D018696:Neuroprotective Agents; C086919:LIGA 20; D005677:G(M1) Ganglioside; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D013110:Sphingosine