Sex-specific differences in hyperoxic lung injury in mice: role of cytochrome P450 (CYP)1A.
Sex-specific differences in hyperoxic lung injury in mice: role of cytochrome P450 (CYP)1A.
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DOI：
10.1016/j.tox.2015.01.019
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发表时间：
2015-05-04
期刊：
影响因子：
4.5
通讯作者：
Moorthy, Bhagavatula
中科院分区：
文献类型：
--
作者：
Lingappan, Krithika;Jiang, Weiwu;Wang, Lihua;Couroucli, Xanthi I.;Moorthy, Bhagavatula
成人和早产儿肺部发病率的性别特异性差异有充分的文献记载。高氧会导致实验动物和人类的肺损伤。细胞色素P450（CYP）1A酶在高氧肺损伤（HLI）动物模型中起重要作用。尚不清楚CYP 1A酶是否导致HLI的性别特异性差异。在这项研究中，我们测试的假设，小鼠将显示性别特异性差异HLI，这种现象将在小鼠缺乏Cyp 1a 1或1a 2的基因改变。将8周龄雄性和雌性野生型（WT）（C57 BL/6 J）小鼠、Cyp 1a 1 −/−和Cyp 1a 2 −/−小鼠暴露于72小时的高氧（FiO 2>0.95）。评估肺损伤和炎症，并在酶活性、蛋白质和mRNA水平上定量肺和肝CYP 1A 1和CYP 1A 2水平。暴露于高氧后，WT雌性动物的肝脏和肺微粒体蛋白显示肺CYP 1A 1（载脂蛋白水平和活性）高于WT雄性动物，高氧暴露后WT雌性动物的肝脏CYP 1A 2 mRNA水平和活性诱导更大。基于性别的雌性优势在Cyp 1a 1 −/−和Cyp 1a 2 −/−小鼠中丧失或逆转。这些发现表明CYP 1A酶在高氧肺损伤的性别特异性调节中起重要作用。
Sex-specific differences in pulmonary morbidity in adults and preterm infants are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. Cytochrome P450 (CYP)1A enzymes have been shown to play a mechanistic role in hyperoxic lung injury (HLI) in animal models. Whether CYP1A enzymes contribute to gender-specific differences in relation to HLI is unknown. In this investigation, we tested the hypothesis that mice will display gender-specific differences in HLI, and that this phenomenon will be altered in mice lacking the genes for Cyp1a1 or 1a2. Eight week-old male and female wild type (WT) (C57BL/6J) mice, Cyp1a1−/−, and Cyp1a2−/− mice were exposed to 72 hours of hyperoxia (FiO2>0.95). Lung injury and inflammation were assessed and pulmonary and hepatic CYP1A1 and CYP1A2 levels were quantified at the enzyme activity, protein and mRNA level. Upon exposure to hyperoxia, liver and lung microsomal proteins showed higher pulmonary CYP1A1 (apoprotein level and activity) in WT females compared to WT males and a greater induction in hepatic CYP1A2 mRNA levels and activity in WT females after hyperoxia exposure. The gender based female advantage was lost or reversed in Cyp1a1−/− and Cyp1a2−/− mice. These findings suggest an important role for CYP1A enzymes in the gender-specific modulation of hyperoxic lung injury.
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影响因子：
3.6
作者：
Couroucli, XI;Welty, SE;Moorthy, B
通讯作者：
Moorthy, B
DOI：
10.1124/jpet.103.059766
发表时间：
2004-08-01
影响因子：
3.5
作者：
Jiang, WW;Welty, SE;Moorthy, B
通讯作者：
Moorthy, B
DOI：
10.1165/rcmb.2009-0210st
发表时间：
2011-05-01
影响因子：
6.4
作者：
Matute-Bello, Gustavo;Downey, Gregory;Villar, Jesus
通讯作者：
Villar, Jesus
影响因子：
--
作者：
NERIISHI, K;FRANK, L
通讯作者：
FRANK, L
影响因子：
4
作者：
Kojima, Misaki;Sekimoto, Masashi;Degawa, Masakuni
通讯作者：
Degawa, Masakuni