Biomaterial Database

PICOT inhibits cardiac hypertrophy and enhances ventricular function and cardiomyocyte contractility. 2006

Dongtak Jeong, and Hyeseon Cha, and Eunyoung Kim, and Misuk Kang, and Dong Kwon Yang, and Ji Myoung Kim, and Pyoung Oh Yoon, and Jae Gyun Oh, and Oliver Y Bernecker, and Susumu Sakata, and Thi Thu Le, and Lei Cui, and Young-Hoon Lee, and Do Han Kim, and Sun-Hee Woo, and Ronglih Liao, and Roger J Hajjar, and Woo Jin Park

Department of Life Science, Global Research Laboratory on Cardiovascular Gene Therapy, Gwangju Institute of Science and Technology, Korea.

Multiple signaling pathways involving protein kinase C (PKC) have been implicated in the development of cardiac hypertrophy. We observed that a putative PKC inhibitor, PICOT (PKC-Interacting Cousin Of Thioredoxin) was upregulated in response to hypertrophic stimuli both in vitro and in vivo. This suggested that PICOT may act as an endogenous negative feedback regulator of cardiac hypertrophy through its ability to inhibit PKC activity, which is elevated during cardiac hypertrophy. Adenovirus-mediated gene transfer of PICOT completely blocked the hypertrophic response of neonatal rat cardiomyocytes to enthothelin-1 and phenylephrine, as demonstrated by cell size, sarcomere rearrangement, atrial natriuretic factor expression, and rates of protein synthesis. Transgenic mice with cardiac-specific overexpression of PICOT showed that PICOT is a potent inhibitor of cardiac hypertrophy induced by pressure overload. In addition, PICOT overexpression dramatically increased the ventricular function and cardiomyocyte contractility as measured by ejection fraction and end-systolic pressure of transgenic hearts and peak shortening of isolated cardiomyocytes, respectively. Intracellular Ca(2+) handing analysis revealed that increases in myofilament Ca(2+) responsiveness, together with increased rate of sarcoplasmic reticulum Ca(2+) reuptake, are associated with the enhanced contractility in PICOT-overexpressing cardiomyocytes. The inhibition of cardiac remodeling by of PICOT with a concomitant increase in ventricular function and cardiomyocyte contractility suggests that PICOT may provide an efficient modality for treatment of cardiac hypertrophy and heart failure.

UI	MeSH Term	Description	Entries
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D011490	Protein Disulfide Reductase (Glutathione)	An enzyme that catalyzes the reduction of a protein-disulfide in the presence of glutathione, forming a protein-dithiol. Insulin is one of its substrates. EC 1.8.4.2.	Glutathione Insulin Transhydrogenase,Glutathione Protein Disulfide Oxidoreductase,Thiol-Disulfide Oxidoreductase,Thiol-Protein Disulfide Oxidoreductase,Disulfide Oxidoreductase, Thiol-Protein,Insulin Transhydrogenase, Glutathione,Oxidoreductase, Thiol-Disulfide,Oxidoreductase, Thiol-Protein Disulfide,Thiol Disulfide Oxidoreductase,Thiol Protein Disulfide Oxidoreductase,Transhydrogenase, Glutathione Insulin
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006332	Cardiomegaly	Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.	Cardiac Hypertrophy,Enlarged Heart,Heart Hypertrophy,Heart Enlargement,Cardiac Hypertrophies,Enlargement, Heart,Heart Hypertrophies,Heart, Enlarged,Hypertrophies, Cardiac,Hypertrophies, Heart,Hypertrophy, Cardiac,Hypertrophy, Heart
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000831	Animals, Newborn	Refers to animals in the period of time just after birth.	Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals