The NADPH oxidase 4 is a major source of hydrogen peroxide in human granulosa-lutein and granulosa tumor cells

التفاصيل البيبلوغرافية
العنوان: The NADPH oxidase 4 is a major source of hydrogen peroxide in human granulosa-lutein and granulosa tumor cells
المؤلفون: Artur Mayerhofer, Theresa Buck, Lars Kunz, Carsten Theo Hack, U. Berg, D. Berg
المصدر: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
سنة النشر: 2018
مصطلحات موضوعية: 0301 basic medicine, inorganic chemicals, Adult, endocrine system, Adolescent, lcsh:Medicine, Aquaporin, Article, 03 medical and health sciences, Paracrine signalling, Young Adult, 0302 clinical medicine, Extracellular, Humans, Phosphorylation, lcsh:Science, Autocrine signalling, Cells, Cultured, Cell Proliferation, Granulosa Cell Tumor, chemistry.chemical_classification, Reactive oxygen species, Multidisciplinary, NADPH oxidase, Granulosa Cells, biology, lcsh:R, Lutein, NOX4, Hydrogen Peroxide, Cell biology, 030104 developmental biology, Enzyme, chemistry, NADPH Oxidase 4, biology.protein, lcsh:Q, Female, Reactive Oxygen Species, 030217 neurology & neurosurgery, Signal Transduction
الوصف: H2O2 is a reactive oxygen species (ROS), which can diffuse away from its site of generation and may act as a cell-to-cell signaling factor. The mechanisms responsible for the generation of H2O2 in human ovarian follicles and possible signaling role(s) of H2O2 are not well known. We identified a source of H2O2, the enzyme NADPH oxidase (NOX) 4, in isolated differentiated, in-vitro fertilisation-derived human granulosa-lutein cells (GCs), in proliferating human granulosa tumour cells (KGN), as well as in situ in cells of growing ovarian follicles. H2O2 was readily detected in the supernatant of cultured GCs and KGN cells. H2O2 levels were significantly lowered by the NOX4 blocker GKT137831, indicating a pronounced contribution of NOX4 to overall H2O2 generation by these cells. We provide evidence that extracellular H2O2 is taken up by GCs, which is facilitated by aquaporins (peroxiporins). We thus conclude that GC-derived H2O2 might act as autocrine/paracrine factor. Addition of H2O2 increased MAPK-phosphorylation in GCs. Moreover, reducing H2O2 production with GKT137831 slowed proliferation of KGN cells. Our results pinpoint NOX4 and H2O2 as physiological players in the regulation of GC functions.
تدمد: 2045-2322
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee409bf17be5a2bfce9025d23272785a
https://pubmed.ncbi.nlm.nih.gov/30837663
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....ee409bf17be5a2bfce9025d23272785a
قاعدة البيانات: OpenAIRE