Our overall goal is to understand what determines whether cells in the intact lung can (do) or cannot (do not) respond to hyperoxia with an increase in antioxidant enzyme (AOE) activity; in essence we wish to understand tolerance to hyperoxia as it occurs in lung cells. Toward this goal we offer three specific aims that are increasingly reductionistic but critically interdependent. We propose: 1) To continue studies using whole rat lungs to detect the level(s) at which the expression of genes for the antioxidant enzymes Cu, Zn superoxide dismutase, Mn superoxide dismutase, catalase, and glutathione peroxidase are regulated (a) to bring about the late gestational increase in activity of these enzymes, and, (b) the increased activity in instances of endogenous or induced tolerance to hyperoxia. 2) To use in situ hybridization and immunolocalization of the AOE, in a quantitative ultrastructural analysis of the intact rat lung, to permit comparison of the AOE response of in vivo cells to hyperoxia with the AOE response to hyperoxia by specific lung cells in culture; our goal here is to evaluate the physiological relevance of the in vitro response of specific cells to hyperoxia. 3) To isolate and clone rat genes for Cu, Zn superoxide dismutase and Mn superoxide dismutase and explore their regulation. Based on our progress to date, the probes we have in hand, and our aggregate experience, we think we are in a favorable position to achieve our aims. Although we are mainly interested in the lung, we think our studies will contribute to an understanding of tolerance to oxidants, which will be of interest to biologists, physiologists, and physicians, and that will eventually be translated into the prevention of 02- toxicity in the lung and perhaps other forms of oxidant damage to other organs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL020366-13
Application #
3564434
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1978-07-01
Project End
1993-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101
Hadden, Helene; Soldin, Steven J; Massaro, Donald (2012) Circadian disruption alters mouse lung clock gene expression and lung mechanics. J Appl Physiol 113:385-92
Massaro, Donald; Massaro, Gloria DeCarlo (2008) Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function. Am J Physiol Lung Cell Mol Physiol 294:L991-7
Massaro, Donald; Clerch, Linda Biadasz; Massaro, Gloria DeCarlo (2007) Estrogen receptor-alpha regulates pulmonary alveolar loss and regeneration in female mice: morphometric and gene expression studies. Am J Physiol Lung Cell Mol Physiol 293:L222-8
Massaro, Donald; Alexander, Emma; Reiland, Kristin et al. (2007) Rapid onset of gene expression in lung, supportive of formation of alveolar septa, induced by refeeding mice after calorie restriction. Am J Physiol Lung Cell Mol Physiol 292:L1313-26
Massaro, Donald; Massaro, Gloria DeCarlo (2007) Developmental alveologenesis: longer, differential regulation and perhaps more danger. Am J Physiol Lung Cell Mol Physiol 293:L568-9
Massaro, Donald; Massaro, Gloria Decarlo (2006) Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice. Am J Physiol Lung Cell Mol Physiol 290:L866-70
Massaro, Donald; Massaro, Gloria Decarlo (2006) Toward therapeutic pulmonary alveolar regeneration in humans. Proc Am Thorac Soc 3:709-12
Chen, Josephine; Zhao, Po; Massaro, Donald et al. (2004) The PEPR GeneChip data warehouse, and implementation of a dynamic time series query tool (SGQT) with graphical interface. Nucleic Acids Res 32:D578-81
Massaro, Donald; Massaro, Gloria DeCarlo (2004) Critical period for alveologenesis and early determinants of adult pulmonary disease. Am J Physiol Lung Cell Mol Physiol 287:L715-7
Clerch, Linda Biadasz; Baras, Alex S; Massaro, Gloria DeCarlo et al. (2004) DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation. Am J Physiol Lung Cell Mol Physiol 286:L411-9

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