TY - JOUR
T1 - Nicotinamide adenine dinucleotide phosphate oxidase is differentially regulated in normal myometrium versus leiomyoma
AU - Fletcher, Nicole M.
AU - Saed, Mohammed G.
AU - Abuanzeh, Suleiman
AU - Abu-Soud, Husam M.
AU - Al-Hendy, Ayman
AU - Diamond, Michael P.
AU - Saed, Ghassan M.
N1 - Publisher Copyright:
© The Author(s) 2014.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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, p47phox, p67phox, and p22phox 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 p67phox were higher while p22phox was lower in fibroid than that in myometrial cells. Hypoxia increased NOX4, DUOX1, and NOXO1 and decreased p22phox 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.
AB - 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, p47phox, p67phox, and p22phox 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 p67phox were higher while p22phox was lower in fibroid than that in myometrial cells. Hypoxia increased NOX4, DUOX1, and NOXO1 and decreased p22phox 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.
KW - NAD(P)H oxidase
KW - hypoxia
KW - leiomyoma
KW - oxidative stress
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U2 - 10.1177/1933719114522552
DO - 10.1177/1933719114522552
M3 - Article
C2 - 24520084
AN - SCOPUS:84905387981
SN - 1933-7191
VL - 21
SP - 1145
EP - 1152
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 9
ER -