NAME: Taylor Robinette
PROJECT TITLE:The Role of Cardiotonic Steroid Marinobufagenin in Uremic Cardiomyopathy Induced by Partial Nephrectomy in Mic
Uremic Cardiomyopathy has been found to develop in chronic renal failure (CRF) patients. Elevated circulating concentrations of cardiotonic steroids such as ouabain and marinobufagenin (MBG), are known to exist in cardiomyopathy and CRF patients. The cardiotonic steroids-mediated Na/K-ATPase signaling plays an important role in CRF-induced uremic cardiomyopathy. This signaling function of the Na/K-ATPase is redox-sensitive and regulated by reactive oxygen species (ROS). Oxidative stress and cardiac fibrosis is a cardiomyopathy’s pathogenic trait (1). To date my mentor’s lab has demonstrated that MBG, signaling through Na+/K+-ATPase induces ROS generation and cardiac fibrosis in rat renal 5/6 partial nephrectomy (PNx) CRF model (2, 3). The objective of this research is to study cardio-protection mechanisms using mouse PNx model developed in our lab. Mouse PNx model can be used to trigger the onset of experimental cardiomyopathy (3). To demonstrated the role of Na/K-ATPase signaling and ROS, the cardiomyopathy progression in mice subjected to PNx will be compared to other experimental groups. (1) Blockage of MBG-stimulated Na/K-ATPase signaling with pNaKtide. pNaKtide is a peptide derived from Na+/K+-ATPase α1 subunit that can block cardiotonic steroids stimulated Na+/K+-ATPase signaling (4); and (2) inhibition of ROS generation with induction of heme-oxygenase-1 (HO-1) by inducer CoPP. HO-1 is a potent inducible anti-oxidative enzyme. Induction of HO-1 has been shown to significantly decrease oxidative stress (5). This will enable us to determine the cardio-protective effects of the pNaKtide and oxidative stress as well as the mechanism relating to the Na+/K+-ATPase signaling pathway.