کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4340840 1295811 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Selective regulation of neurosteroid biosynthesis in human neuroblastoma cells under hydrogen peroxide–induced oxidative stress condition
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Selective regulation of neurosteroid biosynthesis in human neuroblastoma cells under hydrogen peroxide–induced oxidative stress condition
چکیده انگلیسی

Neurosteroid biosynthesis is demonstrated in many species but key factors interacting with neurosteroidogenesis under pathophysiological conditions are unknown. Hydrogen peroxide (H2O2)–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 H2O2 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 H2O2-treatment. Testosterone conversion into estradiol was also inhibited by H2O2. 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 H2O2-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 H2O2-induced stress. Selective targeting of neurosteroidogenic pathways may therefore constitute an interesting strategy against H2O2-evoked neurodegenerative processes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 151, Issue 3, 6 February 2008, Pages 758–770
نویسندگان
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