Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/119898
Title: TARGETING NA+/K+-ATPASE TO TREAT HEART FAILURE AND OSTEOPOROSIS
Authors: HUA FEI
Keywords: Na+/K+-ATPase, antibody, heart failure, osteoporosis, protein phosphatase 2A, oxidative stress
Issue Date: 22-Aug-2014
Citation: HUA FEI (2014-08-22). TARGETING NA+/K+-ATPASE TO TREAT HEART FAILURE AND OSTEOPOROSIS. ScholarBank@NUS Repository.
Abstract: THE ROLE OF NA+-K+-ATPASE (NKA) HAS BEEN WELL ELUCIDATED IN HEART, BUT NOT IN BONES. IN THIS THESIS, IT IS HYPOTHESIZED THAT OXIDATIVE STRESS-INDUCED NKA LOSS IS ASSOCIATED WITH HEART FAILURE AND OSTEOPOROSIS, AND THAT STABILIZATION OF NKA WITH AN ANTIBODY (DR-AB) MAY PROVE THERAPEUTIC TO THE DISEASES. DR-AB PROTECTED CARDIOMYOCYTES AND OSTEOBLASTS FROM OXIDATIVE INJURY BY PREVENTING NKA AGAINST ABERRANT ENDOCYTOSIS DURING OXIDATIVE STRESS. SUPPRESSED PROTEIN PHOSPHATASE 2A WAS RESPONSIBLE FOR MEMBRANE NKA LOSS DUE TO INCREASED PHOSPHORYLATION OF SERINE RESIDUES THAT TRIGGERED ENDOCYTOSIS. DR-AB RESTORED PP2A ACTIVITY AND MAINTAINED MEMBRANE NKA DENSITY. IN HEART, DR-AB REDUCED THE INFARCT SIZE AND IMPROVED HEART CONTRACTILE FUNCTION DURING ISCHEMIA AND MYOCARDIAL INFARCTION-INDUCED HEART FAILURE. IN BONES, DR-AB RESCUED TRABECULAR BONE LOSS, LEADING TO INCREASED BONE STRENGTH. THESE FINDINGS PROVIDE NEW MECHANISTIC INSIGHT TO THE PATHOGENESIS OF HEART FAILURE AND OSTEOPOROSIS, A
URI: http://scholarbank.nus.edu.sg/handle/10635/119898
Appears in Collections:Ph.D Theses (Open)

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