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Etudes de la régulation de la sulfhydryl oxydase QSOX1 et de son implication dans l'apoptose induite par les stress oxydants

Abstract : The quiescin/sulfhydryl oxidase protein QSOX1 is an enzym that catalises disulfide bond formation. In vivo, its substrats are still unknown and its cellular roles remain to be determined. Oxidative stress are especially involved in neurodegenerative diseases. 17b-estradiol (E2) hormone has neuroprotective effects. Our aims were to study the regulation of QSOX1 expression by E2 and QSOX1 involvement in oxidative stress and E2 neuroprotection.
We attempted to establish a model of protection by E2 of PC12/ERa cells submited to oxidative stress induced by H2O2 or Fe(III)-HQ complex. In spite of different tested conditions, no protection by E2 were obtained.
Then, we studied the regulation of QSOX1 expression in brain of ovariectomized female rat treated or not by E2. In three cerebral areas that strongly expressed ERa et ERb, the level of QSOX1 messengers decreased in the presence of E2.
Finally, we studied the QSOX1 involvement in oxidative stress. In PC12 cells submited to oxidative stress, QSOX1 messenger and protein expression increased. After oxidative stress, the viability of MCF-7 cells that overexpressed QSOX1 decreased less stronger than viability of control cells. The decrease of apoptosis is associated to a lesser mitochondria depolarisation in QSOX1 overexpressing MCF-7 cells.
Our works enabled to confirm the estrogeno-dependance of QSOX1 in vivo and to show for the first time the role of QSOX1 in cell protection against oxidative stress-induced apoptosis. These results open new prospects and reinforce the interest of QSOX1 study in the context of neuroprotection by E2.
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https://tel.archives-ouvertes.fr/tel-00311794
Contributor : Carole Morel <>
Submitted on : Thursday, August 21, 2008 - 7:09:01 PM
Last modification on : Tuesday, October 27, 2020 - 2:34:37 PM
Long-term archiving on: : Thursday, June 3, 2010 - 6:41:49 PM

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  • HAL Id : tel-00311794, version 1

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Carole Morel. Etudes de la régulation de la sulfhydryl oxydase QSOX1 et de son implication dans l'apoptose induite par les stress oxydants. Biochimie [q-bio.BM]. Université de Franche-Comté, 2007. Français. ⟨tel-00311794⟩

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