A five year research plan is presented that is targeted towards the general issue of the regulation of protein turnover during pre- and postnatal cardiac development. The overall aims of this study are to examine the relationship between measured rates of total and specific cardiac protein synthesis and degradation, relative mRNA levels, and net protein anabolism and catabolism during late fetal and early postnatal development of the rabbit heart. The techniques to be employed involve the use of continuous and flooding infusion methods of tracer amino acid administration to whole animals, isolation and amino acid analysis of specific cardiac proteins, methods to identify specific proteins and products of cell-free translation derived from cardiac mRNA, and immunochemical, biochemical, and morphological studies of cardiac lysosomal function during fetal and neonatal life. Of particular interest are the adaptive changes in myofibrillar protein synthesis and degradation during growth and remodeling of the left and right ventricles. The hypothesis to be tested is that rates of specific and total cardiac protein degradation as well as synthesis are vitally important to the regulation of cardiac protein mass during physiological adaptation to postnatal hemodynamic changes. Thus, these studies will provide a basis for comparing neonatal functional adaptation to the hypertrophic response of the adult heart to pathological conditions producing pressure or volume overload.
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