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

Neuroscience
Véronique SchaefferA G Mensah-Nyagan

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 prote...Continue Reading

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Citations

Jun 9, 2012·Molecular Neurobiology·Amandine GrimmAnne Eckert
Jul 25, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Christine VenardChristine Patte-Mensah
Dec 15, 2015·Neuroscience and Biobehavioral Reviews·Roberto C MelcangiLuis M Garcia-Segura
Feb 26, 2008·Neurochemistry International·Véronique SchaefferAyikoe G Mensah-Nyagan
Nov 6, 2012·Neurobiology of Aging·Donatella CarusoRoberto C Melcangi

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