肝肺 P4501A 酶在新生儿高氧组织损伤中的作用-猫眼课题宝

肝肺 P4501A 酶在新生儿高氧组织损伤中的作用

批准号：

8519512

负责人：

XANTHI Ioanna COUROUCLI

金额：

$36.17万

依托单位：

BAYLOR COLLEGE OF MEDICINE

依托单位国家：

美国

项目类别：

财政年份：

2009

资助国家：

美国

项目状态：

已结题

起止时间：

2009-09-01 至 2015-07-31

来源：

https://reporter.nih.gov/project-details/8519512

关键词：

Acute Acute Lung Injury Air Animals Biological Assay Bronchopulmonary Dysplasia CYP1A2 gene Cell Communication Cell Culture Techniques Cells Chemosensitization Chronic lung disease Clara cell Corn Oil Cultured Cells Cytochrome P450 Cytochromes Development Disease Electrophoretic Mobility Shift Assay Embryo Enzymes F2-Isoprostanes Fetal Lung Flavonoids Foundations Gene Expression Genes Genetic Transcription Goals Health Hepatic Histology Human Hyperoxia Image Immunohistochemistry In Situ Hybridization Infant Inflammation Inflammatory Injury Irrigation Knock-out Knockout Mice Lipid Peroxidation Liver Luciferases Lung Lung diseases Mediating Messenger RNA Modeling Molecular Mothers Mus Neonatal Newborn Animals Newborn Infant Nuclear Organ Organ failure Oxygen Oxygen Therapy Care Play Premature Infant Prevention Prevention strategy Preventive Production Promoter Regions Proteins Pulmonary Edema Pulmonary Valve Insufficiency Reactive Oxygen Species Regulation Reporter Genes Research Response Elements Retinopathy of Prematurity Reverse Transcriptase Polymerase Chain Reaction Role Running Site-Directed Mutagenesis Southern Blotting Structure of parenchyma of lung Testing Therapeutic Intervention Time Tissues Transcriptional Activation Transgenes Transgenic Mice Transgenic Organisms Western Blotting Wild Type Mouse attenuation chromatin immunoprecipitation cytokine in vivo liver injury lung injury lung maturation morphometry neutrophil novel novel strategies postnatal pregnant prenatal prevent promoter protein expression receptor research study

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DESCRIPTION (provided by applicant): Supplemental oxygen is used extensively in the treatment of pulmonary insufficiency in infants. In premature infants, hyperoxic therapies contribute to the development of bronchopulmonary dysplasia (BPD) and other multi-organ failures. The central hypothesis of the proposed study is that hepatic and pulmonary cytochrome P450 (CYP)1A enzymes play a protective role against acute and long-term injury to lung and other organs by oxygen. The specific aims are: (1) To test the hypothesis that prenatal or postnatal exposure of wild type (WT) (C57BL/6J) mice to the cytochrome P4501A1 (CYP1A1) inducer beta-naphthoflavone (BNF) will result in attenuation or potentiation, respectively, of acute lung and liver injury and abnormal lung maturation resulting from neonatal hyperoxic exposures. Newborn wild type (WT) (C57BL/6J) mice are subjected to prenatal or postnatal treatment with corn oil (vehicle control) or BNF, and newborns will be delivered prematurethe hypothesis that newborn mice lacking the genes for CYP1A1 or the liver- specific CYP1A2 will be more susceptible to acute and long-term lung injury induced by oxygen. Newborn wild type (C57BL/6J), Cyp1a1 (-/-), Cyp1a2 (-/-), or Cyp1a1/1a2 double knockout mice will be exposed to room air or hyperoxia for 7 days, and CYP1A expression and parameters of lung and liver injury will be studied at selected time points. (3) To determine the molecular mechanism of CYP1A1 induction by hyperoxia in the newborn mice in vivo and in cultured cells. This aim has two sub-aims: (i) To test the hypothesis that hyperoxia induces CYP1A1/1A2 gene expression in the newborn through mechanisms involving transcriptional activation of the corresponding promoters. (ii) To determine the mechanisms of induction of human CYP1A1 gene on fetal lung cells. We will test the hypothesis that hyperoxia induces CYP1A1 expression in human or mouse fetal lung cells by interaction of the AHR with specific hyperoxic respopressing the hCYP1A1 in a lung-spcific manner will be less susceptible to hyperoxic lung injury than similarly exposed WT mice. The proposed studies should provide conceptual foundation(s) for the development of novel rational strategies for the prevention and treatment of BPD and other diseases in preterm and term infants. PUBLIC HEALTH RELEVANCE: Supplemental oxygen is used extensively in the treatment of pulmonary insufficiency in infants. In premature infants, hyperoxic therapies contribute to the development of bronchopulmonary dysplasia (BPD) and other multi-organ failures. Using knockout and transgenic mice, and cell culture models, this project is aimed at developing novel approaches for the prevention and treatment of lung (e.g., BPD) and other diseases associated with hyperoxia.

期刊论文(3)

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会议论文

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice.

高氧介导的细胞色素 P4501A1 (CYP1A1) 转录激活可降低新生小鼠对氧介导的肺损伤的易感性。

DOI： 10.1016/j.bbrc.2017.10.166

发表时间： 2018

期刊：

Biochemical and biophysical research communications

影响因子： 3.1

作者：

[Jiang,Weiwu, Maturu,Paramahamsa, Liang,YanhongWei, Wang,Lihua, Lingappan,Krithika, Couroucli,Xanthi]

通讯作者： Couroucli,Xanthi

β-Naphthoflavone treatment attenuates neonatal hyperoxic lung injury in wild type and Cyp1a2-knockout mice.

DOI： 10.1016/j.taap.2017.11.017

发表时间： 2018-01-15

期刊：

Toxicology and applied pharmacology

影响因子： 3.8

作者：

[Lingappan K, Maturu P, Liang YW, Jiang W, Wang L, Moorthy B, Couroucli XI]

通讯作者： Couroucli XI

Role of hepatic and pulmonary P4501A enzymes in neonatal hyperoxic tissue injury

批准号：

8304343
项目类别：
资助金额：

$37.99万
财政年份：

2009
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Role of hepatic and pulmonary P4501A enzymes in neonatal hyperoxic tissue injury

批准号：

7921015
项目类别：
资助金额：

$38.38万
财政年份：

2009
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Role of hepatic and pulmonary P4501A enzymes in neonatal hyperoxic tissue injury

批准号：

7730298
项目类别：
资助金额：

$38.38万
财政年份：

2009
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

6527021
项目类别：
资助金额：

$12.47万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

6549740
项目类别：
资助金额：

$10.01万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

6659754
项目类别：
资助金额：

$12.47万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

6359130
项目类别：
资助金额：

$2.46万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

6944268
项目类别：
资助金额：

$12.47万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

6790654
项目类别：
资助金额：

$12.47万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

Cytochrome P450 regulation by hyperoxia and nitric oxide

批准号：

7292235
项目类别：
资助金额：

$12.96万
财政年份：

2001
负责人：

XANTHI Ioanna COUROUCLI
依托单位：

BAYLOR COLLEGE OF MEDICINE

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