Sarcoplasmic reticulum-associated and protein kinase C-regulated ADP-ribosyl cyclase in cardiac muscle.
Two types of ADP-ribosyl cyclase activity were distinguished in dog and rat cardiac muscles by measuring the enzymatic conversion of NGD (as an NAD analog) into the fluorescent product cyclic GDP-ribose in cardiac muscle subcellular fractions. Both types of activity were confined to membrane fractions isolated from microsomes by sucrose gradient centrifugation. One of the activities co-purified with fractions that were enriched in sarcolemma (SLM), as evidenced by immunodetection of the dihydropyridine receptor, while the other activity was found to co-precipitate with the sarcoplasmic reticulum (SR), that was identified on the basis of its immuno-staining with a ryanodine receptor monoclonal antibody. In certain aspects, the plasma membrane-bound ADP-ribosyl cyclase activity resembled the characteristics of CD38 or CD38-like proteins: it was sensitive to thiols and lectins and was recognized by a monoclonal anti CD38 antibody. The SR enzyme had apparently distinct properties, as it was insensitive to both thiols and lectins and was not recognized by the CD38 antibody. In addition, the SR-associated ADP-ribosyl cyclase was inhibited by endogenous protein kinase C (PKC)-dependent phosphorylation in both dog and rat cardiac SR. The PKC-modulated SR ADP-ribosyl cyclase we describe here might be a principal component of the signal transduction machinery that is responsible for regulation of the intracellular levels of cADPR.
Mészáros
L G
LG
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912, USA.
Wrenn
R W
RW
Váradi
G
G
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D004229:Dithiothreitol / Q000494:pharmacology; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D006150:Guanine Nucleotides / Q000378:metabolism; D006156:Guanosine Diphosphate Sugars / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008562:Membrane Glycoproteins; D009206:Myocardium / Q000201:enzymology*; D009699:N-Glycosyl Hydrolases / Q000276:immunology / Q000378:metabolism*; D009243:NAD / Q000031:analogs & derivatives / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D006150:Guanine Nucleotides; D006156:Guanosine Diphosphate Sugars; D007527:Isoenzymes; D008562:Membrane Glycoproteins; C090657:cyclic guanosine diphosphate-ribose; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; C102728:nicotinamide guanine dinucleotide; D011493:Protein Kinase C; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498156:Cd38 protein, rat; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D004229:Dithiothreitol