title: 17-β-estradiol Decreases Neutrophil Superoxide Production through Rac1.
abstract: Neutrophil granulocytes form the biggest free radical producing system of the human body. The importance of this system in atherosclerotic plaque formation and other free radical mediated disorders is confirmed by both in vivo and in vitro studies. Estrogen's effect on free radical production involves multiple estrogen receptors and occurs both on transcriptional and on protein phosphorylational level. Estrogen decreases the superoxide production of neutrophil granulocytes in such a short time frame it is unlikely to be mediated by transcription regulation. We investigated the underlying mechanism through which the mentioned estrogen effect takes place using an immunabsorption-based method. Phosphorylation data of 43 different messenger proteins were used for pathway analysis. The newly identified pathway involved largely second messengers from previously described non-genomic estrogen effects and affected superoxide production via Rac1 - an important regulator of free radical production and chemotaxis. Selective inhibition of the participating second messengers altered superoxide production in the predicted direction confirming that this pathway is at least partly responsible for the effect of 17-β-estradiol on chemoattractant induced superoxide production.
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Marczell
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Tűzoltó u. 37-47., H-1094 Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Hrabak
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Nyiro
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Patocs
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Stark
authors.affiliation: Faculty of Health and Public Services, Institute of Health Informatics Development and Further Training, Semmelweis University, Ulloi ut 78/b, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Dinya
authors.affiliation: Office for Research Groups Attached to Universities and Other Institutions of the Hungarian Academy of Sciences, Molecular Medicine Research Group; H-1088, Budapest, Szentkirályi str. 46. Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Kukor
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Nagyvárad tér 4., H-1089 Budapest, Hungary.
authors.forename: S
authors.initials: S
authors.lastname: Toth
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Tulassay
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Racz
authors.affiliation: 2nd Department of Medicine Semmelweis University; Szentkirályi utca 46., H-1088 Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Bekesi
mesh_terms: D000328:Adult; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C107953:RAC1 protein, human; D013481:Superoxides; D004958:Estradiol; D020830:rac1 GTP-Binding Protein