Identification and characterization of G protein-regulated phospholipase C in human myocardium. 1996

P Schnabel, and H Gäs, and T Nohr, and M Camps, and M Böhm
Klinik III für Innere Medizin, Universität zu Köln, Germany.

The generation of the second messengers inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG) by phosphoinositide-specific phospholipases C (PLCs) is a key mechanism by which many cellular functions such as intracellular calcium handling or growth and differentiation are modulated. In the myocardium, PLC plays a role in the mediation of positive inotropic effects and is possibly involved in the pathogenesis of myocardial hypertrophy. Among the variety of PLC isozymes known, the PLC beta family is regulated by heterotrimeric G proteins. The aim of the present study was to identify and to characterize the PLC beta isoform present in human myocardium. PLC activity in human myocardial membranes was dependent on the presence of Ca2+. Interestingly, PLC was markedly stimulated by GTP gamma S, used as an activator of G proteins. This stimulation was completely abolished by GDP. However, purified alpha-subunits from retinal transducin (alpha 1), used as scavengers of free beta gamma-subunits, did not abolish this effect indicating GTP gamma S stimulation being mediated by G protein alpha-subunits. PLC activity was also stimulated by G protein beta gamma-subunits purified from bovine retina (beta gamma t). This stimulation was completely blocked by addition of purified alpha t. Reverse transcriptions and polymerase chain reactions (RT-PCR) provided evidence for PLC beta 1 mRNA being expressed in human myocardium, whereas PCR products corresponding to PLC beta 2 and PLC beta 3 mRNAs were not detected. It is concluded that PLC beta 1 mRNA is expressed in human myocardium. The functional properties of human myocardial PLC activity correspond well to the properties established for PLC beta 1, i.e. sensitivity to G protein alpha-as well as beta gamma-subunits. The presence of other as yet unidentified PLC isozymes is nevertheless possible. The identification of the PLC beta isozyme present in human myocardium and the understanding of its regulation by G protein subunits sets the stage for the investigation of possible involvement of this system in the pathophysiology of myocardial hypertrophy.

UI MeSH Term Description Entries
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010738 Type C Phospholipases A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS. Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D016244 Guanosine 5'-O-(3-Thiotriphosphate) Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes. GTP gamma S,Guanosine 5'-(gamma-S)Triphosphate,gamma-Thio-GTP,GTPgammaS,Guanosine 5'-(3-O-Thio)Triphosphate,gamma S, GTP,gamma Thio GTP
D019204 GTP-Binding Proteins Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-. G-Proteins,GTP-Regulatory Proteins,Guanine Nucleotide Regulatory Proteins,G-Protein,GTP-Binding Protein,GTP-Regulatory Protein,Guanine Nucleotide Coupling Protein,G Protein,G Proteins,GTP Binding Protein,GTP Binding Proteins,GTP Regulatory Protein,GTP Regulatory Proteins,Protein, GTP-Binding,Protein, GTP-Regulatory,Proteins, GTP-Binding,Proteins, GTP-Regulatory

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