RESUMO
High plasma levels of homocysteine (Hcy) promote the progression of neurodegenerative diseases. However, the mechanism by which Hcy mediates neurotoxicity has not been elucidated. We observed that upon incubation with Hcy, the viability of a neuroblastoma cell line Neuro2a declined in a dose-dependent manner, and apoptosis was induced within 48 h. The median effective concentration (EC50) of Hcy was approximately 5 mM. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) nuclear translocation and acylation has been implicated in the regulation of apoptosis. We found that nuclear translocation and acetylation of GAPDH increased in the presence of 5 mM Hcy and that higher levels of acetyltransferase p300/CBP were detected in Neuro2a cells. These findings implicate the involvement of GAPDH in the mechanism whereby Hcy induces apoptosis in neurons. This study highlights a potentially important pathway in neurodegenerative disorders, and a novel target pathway for neuroprotective therapy.
Assuntos
Animais , Coelhos , Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Homocisteína/farmacologia , Acetilação , Acetiltransferases/análise , Fatores de Tempo , Contagem de Células , Extratos Celulares/química , Núcleo Celular/metabolismo , Sobrevivência Celular/fisiologia , Indução Enzimática , Western Blotting , Imunofluorescência , Apoptose/fisiologia , Fármacos Neuroprotetores/administração & dosagem , Linhagem Celular Tumoral , Fatores de Transcrição de p300-CBP/metabolismo , Homocisteína/administração & dosagemRESUMO
Objective To study the active compounds of the sea cucumber Colochirus anceps.Methods The compounds were isolated and purified from the low-polarity part of EtOH extract of the sea cucumber,and their structures were established by a combination of spectroscopic analysis,chemical transformation,and other chemical evidence.Results Four compounds were isolated and their structures were established as 1-O-?-D-glucopyranosyl-(2S,3R,4E,8E)-2-docosanoylamino-13-methyl-4,8-hexadecadiene-1,3-diol(Ⅰ),1-O-?-D-glucopyranosyl-(2S,3R,4E,8E)-2-[(2R)-2-hydroxydocosa-noylamino]-13-methyl-4,8-hexadecadiene-1,3-diol(Ⅱ),1-O-?-D-glucopyranosyl-(2S,3R,4E,8E)-2-[(2R)-2-hydroxy-tricosanoylamido]-13methyl-4,8-hexadecadiene-1,3-diol(Ⅲ),and 1-O-?D-glucopyranosyl-(2S,3R,4E,8E)-2-[(2R)-2-hydroxy-tetracosanoylamino]-13-methyl-4,8-hexadecadiene-1,3-diol(Ⅳ).Conclusion Four new cerebrosides are isolated from the sea cucumber C.anceps for the first time.