title: Nicotinamide adenine dinucleotide phosphate oxidase is differentially regulated in normal myometrium versus leiomyoma.
abstract: Uterine fibroids are the most common benign tumor in women. The goal of this study was to investigate whether nicotinamide adenine dinucleotide phosphate oxidase (NOX), a major source of superoxide and subsequent oxidative stress, was differentially regulated in myometrium versus leiomyoma. Expression levels of NOXs1-5, dual oxidase (DUOX), DUOX2, NOX organizer (NOXO) 1, NOX activator 1, p47(phox), p67(phox), and p22(phox) were determined in cells treated with hypoxia by real-time reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry in tissues. Expression of NOX4 increased in fibroid compared to myometrial tissues and cells. The NOX2, DUOX1, and p67(phox) were higher while p22(phox) was lower in fibroid than that in myometrial cells. Hypoxia increased NOX4, DUOX1, and NOXO1 and decreased p22(phox) in myometrial and reduced DUOX1 in fibroid cells. The NOX1, NOX3, NOX5, and DUOX2 were undetectable. Fibroid cells are characterized by a unique NOX profile, which promotes a severe prooxidant state that may be responsible for their development. Targeting these subunits may be beneficial for future therapeutic interventions.
authors: Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
authors: Nicole M
authors: NM
authors: Fletcher
authors: Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
authors: Mohammed G
authors: MG
authors: Saed
authors: Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
authors: Suleiman
authors: S
authors: Abuanzeh
authors: Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
authors: Husam M
authors: HM
authors: Abu-Soud
authors: Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN, USA.
authors: Ayman
authors: A
authors: Al-Hendy
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, GA, USA.
authors: Michael P
authors: MP
authors: Diamond
authors: Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA gsaed@med.wayne.edu.
authors: Ghassan M
authors: GM
authors: Saed
mesh_terms: D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology* / Q000473:pathology; D008562:Membrane Glycoproteins; D009215:Myometrium / Q000201:enzymology* / Q000473:pathology; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000502:physiology*; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human
keywords: NAD(P)H oxidase; hypoxia; leiomyoma; oxidative stress