Ischemia-reperfusion causes a restricted proteolytic modification of cardiac TnT in the heart. This proteolytic cleavage specifically removes the N-terminal modulating segment of TnT preserving the TnT core structure and function. To investigate whether the restricted proteolytic removal of the N-terminal segment of cardiac TnT is a post-translational regulation in response to ischemia reperfusion, the sponsor's lab has constructed transgenic mice over-expressing the N-terminal truncated cardiac TnT in the heart. Characterization of this mouse model would determine the functional significance of this proteolytic modification in the pathophysiology of ischemic heart disease. This postdoctoral training proposal focuses on biochemical and physiological characterizations of the transgenic mouse hearts. Ca(2+) regulation of myofibril actomyosin ATPase activity, cardiomyocyte contractility, and working heart function will be studied. By using the transgenic mouse heart as an integrated experimental system, the results will contribute to the understanding of cardiac muscle contraction and adaptation in ischemic heart disease. ? ? ?
| Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert et al. (2015) Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice. Am J Physiol Lung Cell Mol Physiol 308:L464-78 |
| Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert et al. (2012) Neonatal mice genetically modified to express the elastase inhibitor elafin are protected against the adverse effects of mechanical ventilation on lung growth. Am J Physiol Lung Cell Mol Physiol 303:L215-27 |
| Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert et al. (2011) Inhibiting lung elastase activity enables lung growth in mechanically ventilated newborn mice. Am J Respir Crit Care Med 184:537-46 |
| Mokres, Lucia M; Parai, Kakoli; Hilgendorff, Anne et al. (2010) Prolonged mechanical ventilation with air induces apoptosis and causes failure of alveolar septation and angiogenesis in lungs of newborn mice. Am J Physiol Lung Cell Mol Physiol 298:L23-35 |
