Structural and enzymatic proteins play an important role in determining the physiological and biochemical integrity of the lung at both the tissue and cellular levels. Alterations in the levels of these components may thus determine developmental, physiological and pathological changes in the lung. Nevertheless, little information is available regarding the basic control of synthesis or degradation of lung proteins. Thus, it is proposed to investigate the hormonal regulation of protein synthesis in lung tissue and, in parallel, in a specific lung cell type, the type II pneumocyte. The latter goal will be reached using type II cells in culture, as well as using lungs perfused in situ, by employing immunological techniques to investigate synthesis of a type II cell-specific protein recently identified and characterized in this laboratory. The effects of factors which modify the metabolism of whole lung and type II cell-specific proteins will be localized to specific steps in the pathway of protein synthesis. Furthermore, rates of protein degradation will be monitored to determine the role of alterations in this process in affecting changes in levels of lung proteins. Investigation of the control of protein metabolism at the whole-tissue and -cell levels in parallel with studies of the synthesis of type II cell-specific proteins will begin to resolve the issues of potential hetergeneity in metabolic regulation among lung cell types, as well of alterations which may occur when cells are placed in primary culture. In addition, the mechanism by which lung growth is accelerated following unilaterl pneumonectomy will be investigated. Understanding the mechanism of this growth, which involves rapid accumulation of protein and is thought to be under hormonal control, will provide further insight into the physiological role of hormones and other factors, including a growth factor which appears to be present in the serum of pneuymonectomized rats, in the regulation of protein metabolism in whole lung tissue and in type II cells. Understanding of factors which modify turnover of lung cell proteins and of specific proteins important to lung function will contribute to increased knowledge of the physiological chemistry of the normal lung and thus, to a better understanding of the mechanisms underlying pulmonary disease.
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