Division of Cardiocirculatory Signaling
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Welcome to our laboratory!

Our laboratory specializes in cardiovascular pharmacology and physiology.  We especially focus on two essential signaling mediators, calcium ion (Ca2+) and reactive oxygen species (ROS), and aims to reveal the molecular mechanism underlying systemic control of cardiocirculatory homeostasis, and develop or foster riskless drugs that have the ability to normalize aberrant signaling in the cardiociculatory system.

 
Reserch

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Evidence-based medicine (EBM) has been long established as a novel strategy for the treatment of chronic cardiovascular diseases.  A typical successful example is the discovery of beta-adrenergic receptor blocker, a cardiodepressant, is now applicable for the treatment of heart failure.  The concept has provided understanding of the molecular basis underlying systemic control of cardiocirculatory homeostasis by neurohumoral factors, growth factors and metabolites.  Our laboratory focuses on intracellular signaling pathways activated by these factors, and aims to develop or foster riskless drugs that have the ability to normalize aberrant signaling in the cardiovascular system.  Following are two research projects currently being undertaken in our laboratory;

1.Reduction/oxidation (redox) regulation of cardiovascular functions by hydrogen sulfide.
This study covers the field of chemical biology where chemistry is integrated with biology through application of chemical techniques and tools to the study and manipulation of biological system.  We recently found that hydrogen sulfide anion (H2S/HS-) suppressed chronic heart failure by reducing oxidative stress via nucleophilic reaction to ROS-derived electrophilic byproducts (Figure 1).  As H2S per se is a toxic gas, we are searching an in vivo substrate which has a potent nucleophilic property like H2S/HS-


Figure 1.  Chemistry-based oxidative modification of protein cystine thiol and its suppression by H2S/HS-

 

2.Mechanism underlying systemic control of cardiocirculatory homeostasis by
Ca2+ channels

Autonomic nervous system and renin-angiotensin-aldosterone system play a critical role in regulating cardiovascular homeostasis.  Ca2+ influx through Ca2+ channels on the plasma membrane regulates the secretions of these neurohumoral factors.  We have revealed that receptor-activated cation channels (TRPC3/6) work as a key player in the development of cardiac hypertrophy, and newly found that TRPC3/6 channels also regulate internal secretions essential for systemic control of cardiocirculatory homeostasis using TRPC3/6-deficient mice (Figure 2).




Figure 2. Regulation of cardiovascular homeostasis by unique Ca2+ channels expressed in several secretory organs.

 
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