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Selective regulation of neurosteroid biosynthesis in human neuroblastoma cells under hydrogen peroxide-induced oxidative stress condition

Schaeffer, V. and Patte-Mensah, C. and Eckert, A. and Mensah-Nyagan, A. G.. (2008) Selective regulation of neurosteroid biosynthesis in human neuroblastoma cells under hydrogen peroxide-induced oxidative stress condition. Neuroscience, Vol. 151. pp. 758-770.

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Official URL: http://edoc.unibas.ch/dok/A6006121

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Abstract

Neurosteroid biosynthesis is demonstrated in many species but key factors interacting with neurosteroidogenesis under pathophysiological conditions are unknown. Hydrogen peroxide (H(2)O(2))-induced oxidative stress is an etiological factor involved in several disorders. We hypothesized that, if neurosteroidogenesis is a pivotal mechanism for nerve cell protection or viability, it might be selectively regulated under oxidative stress condition. To check our hypothesis, we investigated H(2)O(2) effects on neurosteroidogenesis in human neuroblastoma SH-SY5Y cells. Pulse-chase, high performance liquid chromatography and flow-scintillation analyses showed that, along neurosteroidogenic pathways converting pregnenolone into various neurosteroids, only estradiol synthesis selectively decreased in SH-SY5Y cells after H(2)O(2)-treatment. Testosterone conversion into estradiol was also inhibited by H(2)O(2). Real-time reverse transcription-polymerase chain reaction revealed aromatase gene repression in SH-SY5Y cells 12 h after the oxidative stress onset. Consistently, viability assays showed that chronic inhibition of aromatase activity by letrozole killed neuroblastoma cells. A 12-h pretreatment of SH-SY5Y cells with estradiol was protective against H(2)O(2)-induced death. In addition, estradiol was also capable of rescuing markedly neuroblastoma cells from letrozole-evoked death. Altogether, these results suggest that endogenous estradiol formation is pivotal for SH-SY5Y cell viability. Serum deprivation-evoked stress, which also killed SH-SY5Y cells, unaffected neurosteroidogenesis, indicating that inhibitory effect on neuroprotective-neurosteroid estradiol biosynthesis is specific for H(2)O(2)-induced stress. Selective targeting of neurosteroidogenic pathways may therefore constitute an interesting strategy against H(2)O(2)-evoked neurodegenerative processes.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0306-4522
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Dec 2012 13:03
Deposited On:07 Dec 2012 12:59

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