Durham Research Center 3047
Phone: 402- 559-9018
Keywords: Diabetes, heart, muscle contraction, calcium cycling proteins ryanodine receptors, Ca2+-ATPase, myosin heavy chain, echocardiography, calcium transientsDr. Bidasee in his own words.
Research Interests: Our long term goals are to better understand (i) molecular and cellular mechanisms responsible for cardiovascular complications in individuals with diabetes mellitus (DM), and (ii) to identify therapeutic strategies that could be used to slow their progressions.
In spite of an armamentarium of glucose-lowering agents, glucose monitoring devices, food management, and exercise strategies, individuals with DM are continuing to develop cardiovascular diseases at rates 3-4 times higher than that of the general population. There are also no specific pharmacological agents available to prevent the development of these cardiovascular diseases.
Reactive carbonyl species (RCS) are small mono- and di-carbonyl molecules generated from glucose and lipid metabolisms. These electrophilic molecules play important roles in regulating key physiologic functions including growth, differentiation, proliferation, and apoptosis and their cellular levels are tightly regulated to minimize undesired effects. In individuals with DM cellular levels of “free” RCS increases. When unregulated, RCS irreversibly react with susceptible basic amino acid residues on proteins to alter their functions. They also perturb cellular Ca2+ homeostasis, increase production of pro-inflammatory mediators and oxidative stress form adducts with DNA.
Better understanding how to regulate RCS levels in diabetes could help alleviate cardiovascular complications in diabetes.
Significance: Not only will our research lead to improvements in the quality of life for diabetic patients but also help control the escalating economic cost medical expenditure and loss productivity, which was estimated at $150 billion annually.
Moore CJ, Shao CH, Nagai R, Kutty S Singh J and Bidasee KR. Malondialdehyde and 4-hydroxynonenal adducts are not formed on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) in diabetes. Mol Cell Biochem. 376(1-2):121-35, 2013.
Shao C-H, Tian C, Ouyang S, Moore CJ, Alomar F, Nemet I, D’Souza A, Nagai R, Kutty S, Rozanski GJ, Ramanadham S, Singh J and Bidasee KR. Cabonylation induces heterogeneity in cardiac ryanodine receptor function during diabetes. Mol Pharmacol 82: 383-399, 2012.
Shao CH, Capek HL, Patel KP, Wang M, Tang K, Desouza C, Nagai R, Mayhan W, Periasamy M, Bidasee KR. Carbonylation contributes to SERCA2a activity loss and diastolic dysfunction in a rat model of Type 1 diabetes. Diabetes 60:947-959, 2011.
Tian C, Shao CH, Moore CJ, Kutty S, Walseth T, DeSouza C, Bidasee KR. Gain-of-function of cardiac ryanodine receptor in a rat model of type 1 diabetes. Cardiovasc Res 91: 300-309, 2011.
Desouza CV, Hamel FG, Bidasee KR, O'Connell K. Role of inflammation and insulin resistance in endothelial progenitor cell dysfunction. Diabetes 60: 1286-1294, 2011.
Shao CH, Rozanski GJ, Nagai R, Stockdale FE, Patel KP, Wang M, Singh J, Mayhan WG, Bidasee KR. Carbonylation of myosin heavy chains in rat heart during diabetes. Biochem Pharmacol. 2010;80(2):205-17.
Work in our lab has been funded by the National Institutes of Health.
Additional publications in PubMed
Dr. Bidasee's biographical information.