Nicotinamide Adenine Dinucleotide Phosphate Oxidase Is Differentially Regulated in Normal Myometrium Versus Leiomyoma
Nicotinamide Adenine Dinucleotide Phosphate Oxidase Is Differentially Regulated in Normal Myometrium Versus Leiomyoma
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DOI：
10.1177/1933719114522552
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发表时间：
2014-09-01
影响因子：
2.9
通讯作者：
Saed, Ghassan M.
中科院分区：
文献类型：
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作者：
Fletcher, Nicole M.;Saed, Mohammed G.;Saed, Ghassan M.
子宫肌瘤是女性最常见的良性肿瘤。本研究的目的是调查烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）（超氧化物和随后的氧化应激的主要来源）在子宫肌层与平滑肌瘤中是否受到差异性调节。通过组织中的实时逆转录聚合酶链反应、蛋白质印迹和免疫组织化学测定缺氧处理的细胞中NOXs1-5、双氧化酶（DUOX）、DUOX2、NOX组织者（NOXO）1、NOX激活剂1、p47（phox）、p67（phox）和p22（phox）的表达水平。与子宫肌层组织和细胞相比，肌瘤中 NOX4 的表达增加。肌瘤细胞中NOX2、DUOX1和p67(phox)高于子宫肌层细胞，p22(phox)低于子宫肌层细胞。缺氧使子宫肌层中的 NOX4、DUOX1 和 NOXO1 增加，p22(phox) 减少，肌瘤细胞中 DUOX1 减少。 NOX1、NOX3、NOX5 和 DUOX2 无法检测到。肌瘤细胞具有独特的 NOX 特征，可促进严重的促氧化状态，这可能是其发育的原因。针对这些亚基可能有利于未来的治疗干预。
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.