title: Protective effects of 27- and 24-hydroxycholesterol against staurosporine-induced cell death in undifferentiated neuroblastoma SH-SY5Y cells.
abstract: Alterations in cholesterol metabolism have been linked to several neurodegenerative disorders, including Alzheimer's disease, multiple sclerosis and Parkinson's disease. Brain cholesterol is metabolized to the oxysterols 24-hydroxycholesterol and 27-hydroxycholesterol. Disturbed levels of these oxysterols are found in neurodegenerative conditions. In the current study we examined the effects of 27- and 24-hydroxycholesterol on viability of human neuroblastoma SH-SY5Y cells treated with staurosporine, a toxic substance that induces apoptosis. Analyses using MTT assay and measurement of lactate dehydrogenase release showed that presence of 27-hydroxycholesterol counteracted the toxic effects of staurosporine on these cells. Also, 27-hydroxycholesterol significantly decreased the staurosporine-mediated induction of caspase-3 and -7, known to be important in apoptotic events. 24-Hydroxycholesterol had similar effects on viability as 27-hydroxycholesterol in low concentrations, although in higher concentrations this oxysterol exacerbated the toxic effects of staurosporine. From these findings it may be concluded that effects of oxysterols on cellular viability are strongly dependent on the concentration and on the type of oxysterol. Previous studies on oxysterols have reported that these compounds are pro-apoptotic or trigger pathological changes that result in neurodegeneration. The present data indicate that, during some conditions, oxysterols may have neuroprotective effects.
authors.affiliation: Department of Pharmaceutical Biosciences, Box 591, Uppsala University, S-751 24 Uppsala, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Emanuelsson
authors.forename: Maria
authors.initials: M
authors.lastname: Norlin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D006888:Hydroxycholesterols; D018696:Neuroprotective Agents; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053179:Caspase 7; D019311:Staurosporine