Durham Research Center 3047
985800 Nebraska Medical Center
Omaha, NE 68198-5800
Keywords: Diabetes, heart, muscle contraction, calcium cycling proteins ryanodine receptors, Ca2+-ATPase, myosin heavy chain, echocardiography, calcium transients
Dr. Bidasee honored for Most Promising New Invention by UNeMed.
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.
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.
A better understanding of how to regulate RCS levels in diabetes could help alleviate cardiovascular complications in diabetes.
- Singh RM, Waqar T, Howarth FC, Adeghate E, Bidasee K, Singh J: Hyperglycemia-induced cardiac contractile dysfunction in the diabetic heart. Heart failure reviews 2018, 23:37-54.
- Alomar F, Singh J, Jang HS, Rozanzki GJ, Shao CH, Padanilam BJ, Mayhan WG, Bidasee KR: Smooth muscle-generated methylglyoxal impairs endothelial cell-mediated vasodilatation of cerebral microvessels in type 1 diabetic rats. British journal of pharmacology 2016, 173:3307-26. PMID: 27611446. PMC5738666.
- Tian C, Shao CH, Padanilam C, Ezell E, Singh J, Kutty S, Bidasee KR: CCDI: a new ligand that modulates mammalian type 1 ryanodine receptor (RyR1). British journal of pharmacology 2014, 171:4097-111. PMID: 24819467. PMC4243982.
- Tian C, Alomar F, Moore CJ, Shao CH, Kutty S, Singh J, Bidasee KR: Reactive carbonyl species and their roles in sarcoplasmic reticulum Ca2+ cycling defect in the diabetic heart. Heart failure reviews 2014, 19:101-12. PMID: 23430128. PMC4732283.
- Palsamy P, Bidasee KR, Ayaki M, Augusteyn RC, Chan JY, Shinohara T: Methylglyoxal induces endoplasmic reticulum stress and DNA demethylation in the Keap1 promoter of human lens epithelial cells and age-related cataracts. Free radical biology & medicine 2014, 72:134-48. PMC4410980.
- Lei X, Bone RN, Ali T, Zhang S, Bohrer A, Tse HM, Bidasee KR, Ramanadham S: Evidence of contribution of iPLA2beta-mediated events during islet beta-cell apoptosis due to proinflammatory cytokines suggests a role for iPLA2beta in T1D development. Endocrinology 2014, 155:3352-64. PMID: 24746615. PMC4138580.
- Zheng MQ, Li X, Tang K, Sharma NM, Wyatt TA, Patel KP, Gao L, Bidasee KR, Rozanski GJ: Pyruvate restores beta-adrenergic sensitivity of L-type Ca(2+) channels in failing rat heart: role of protein phosphatase. American journal of physiology Heart and circulatory physiology 2013, 304:H1352-60. PMID: 23504177. PMC3652062.
- 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. PMID: 23354458. PMCID: PMC4720987.
- 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. PMID: 22648972. PMCID: PMC3422706 .
- 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. PMID: 21300842. PMCID: PMC3046856
- 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. PMID: 21421556. PMCID: PMC3125072.