Research

2011 research

My laboratory is interested in various aspects of vascular biology, in particular vascular disorders associated with menopause, diabetes and hypertension. Calmodulin is the most important transducer of intracellular Ca²⁺ signals by virtue of its requirement for the functions of numerous cellular proteins and its insufficient expression for all its targets. Modulating aspects of calmodulin-dependent signaling thus represents therapeutic potential for many cardiovascular disorders. We use combination of molecular, cellular and biochemical approaches coupled with multi-wavelength intracellular imaging techniques to investigate the mechanisms and therapeutic options for alterations in calmodulin-dependent signaling associated with menopause, diabetes and hypertension. Currently we are (1) Elucidating signal transduction via a novel calmodulin-binding protein we recently identified that has been implicated in many cardiovascular functions; (2) Investigating intercellular interactions via calmodulin among the main cell types of the vasculature using a novel model we recently developed; and (3) Investigating the effects of sex hormones and their deprivation on intracellular signaling via Ca²⁺ and calmodulin as well as intercellular interactions in the vasculature.

Publications

Tran QK, Leonard J, Black DJ, Persechini A. Effects of combined phosphorylation at Ser-617 and Ser-1179 in endothelial nitric oxide synthase on EC50(Ca2+) values for calmodulin binding and enzyme activation. J. Biol Chem; 284(18): 11892-11899., 2009

Tran QK, Leonard J, Black DJ, Persechini A. Phosphorylation within an Autoinhibitory Domain in Endothelial Nitric Oxide Synthase Reduces the Ca2+ Concentrations Required for Calmodulin To Bind and Activate the Enzyme. Biochemistry;47(28):7557-66., 2008

Tran Q-K, Watanabe H. Calcium signaling in the endothelium. (Book Chapter) In: The Vascular Endothelium (Handbook of Experimental Pharmacology, Vol. 176: 145-187; 2006) Edited by Moncada S. and Higgs A. ISBN: 3- 540-32966-8., 2006

Tran Q-K, Black DJ, Persechini A. Dominant affectors in the calmodulin network shape the time courses of target responses in the cell. Cell Calcium;37(6):541-553., 2005

Black DJ, Tran Q-K, Persechini A. Monitoring the total available calmodulin concentration in intact cells over the physiological range in free Ca2+. Cell Calcium; 35(5):415-25 , 2004

Takeuchi K, Watanabe H, Tran Q-K, Ozeki M, Sumi D, Hayashi T, Iguchi A, Ignarro LJ, Ohashi K, Hayashi H. Nitric oxide: inhibitory effects on endothelial cell calcium signaling, prostaglandin I2 production and nitric oxide synthase expression. Cardiovasc Res;62:194-201., 2004

Tran Q-K, Watanabe H. Myosin Light Chain Kinase in Endothelial Cell Calcium Signaling and Endothelial Functions. Book Chapter In: Atherosclerosis, Hypertension and Diabetes (Book series: Progress in Experimental Cardiology. Vol. 8, pp 163-174; 2003). Edited by Pierce G.N., Nagano M, Zahradka P, and Dhalla NS. Kluwer Academic/Plenum Publishers. ISBN 1-4020-7311-9., 2003

Tran Q-K, Black DJ, Persechini A. Intracellular coupling via limiting calmodulin. J. Biol. Chem.;278(27):24247- 50., 2003

Takeuchi K, Watanabe H, Tran Q-K, Ozeki M, Uehara A, Katoh H, Satoh H, Terada H, Hayashi H. Effects of cytochrome P450 inhibitors on agonist-induced Ca2+ responses and production of NO and PGI2 in vascular endothelial cells. Mol Cell Biochem.;248(1-2):129-34., 2003

Watanabe H, Ohashi K, Takeuchi K, Yamashita K, Yokoyama T, Tran Q-K, Satoh H, Terada H, Ohashi H, Hayashi H. Sildenafil for primary and secondary pulmonary hypertension. Clin Pharmacol Ther.;71(5):398-402., 2002

Tran Q-K, Watanabe H, Le H-Y, Takeuchi K, Hattori Y, Tomioka H, Ohashi K, Hayashi H. Insulin inhibits coronary endothelial cell Ca2+ entry and coronary artery relaxation. J Cardiovas Pharmacol; 38 (6):885-892., 2001

Tran Q-K, Watanabe H, Le H-Y, Ling P, Seto M, Takeuchi K, Ohashi K. Myosin light chain kinase regulates capacitative Ca2+ entry in human monocytes/macrophages. Arterioscler Thromb Vasc Biol;21; 509-515., 2001

Watanabe H, Tran Q-K, Takeuchi K, Fukao M, Liu MY, Kanno M, Hayashi T, Iguchi A, Seto M, Ohashi K. Myosin light-chain kinase regulates endothelial Ca2+ entry and endothelium-derived vasodilation. FASEB J.; 15 (2):282-284., 2001

Tomioka H, Hattori Y, Fukao M, Watanabe H, Akaishi Y, Sato A, Tran Q-K, Sakuma I, Kitabatake A, Kanno M. Role of endothelial Ni2+-sensitive Ca2+ entry pathway in regulation of EDHF in porcine coronary artery. Am J Physiol Heart Circ Physiol; 280:H730-H737., 2001

Tran Q-K, Ohashi K, Watanabe H. Calcium signalling in endothelial cells. (Review) Cardiovasc Res.;48(1):13- 22., 2000

Tran Q-K, Watanabe H, Le H-Y, Yang J, Takeuchi K, Kadomatsu K, Muramatsu T, Ohashi K. Midkine inhibits bradykinin-induced endothelial Ca2+ signaling and nitric oxide production. Biochem Biophys Res Commun.; 276;830-836., 2000

Fukao M, Hattori H, Sato A, Liu MY, Watanabe H, Tran Q-K, Kanno M. Relationship between NaF- and thapsigargin-induced endothelium-dependent hyperpolarization in rat mesenteric artery. Brit J Pharmacol.;126:1567-1574., 1999

Watanabe H, Takahashi R, Tran Q-K, Takeuchi K, Kosuge K, Satoh H, Uehara A, Terada H, Hayashi H, Ohno R, Ohashi K. Increased cytosolic Ca2+ concentration in endothelial cells by calmodulin antagonists. Biochem Biophys Res Commun.;265:697-702., 1999

Tran Q-K, Watanabe H, Zhang XX, Takahashi R, Ohno R. Involvement of myosin light chain kinase in chloride- sensitive Ca2+ influx in porcine aortic endothelial cells. Cardiovasc Res.;44:623-631., 1999