Intracellular renin and the nature of intracrine enzymes.
Recently, the binding of renin and prorenin to cellular receptors with the subsequent generation of second messengers and the production of physiological effects has been demonstrated. In addition, the internalization of prorenin by target cells has been associated with increased cellular synthesis of angiotensin and cardiac pathology. Also, a renin transcript lacking the sequences encoding a secretory signal has been reported, and this transcript appears to produce a renin that acts in the cell that synthesized it. Some years ago, we coined the term intracrine for a peptide hormone or factor that acts in the intracellular space either after internalization or retention in its cell of synthesis. Thus defined, a wide variety of peptides display intracrine functionality, including hormones, growth factors, transcription factors, and enzymes. For example, considerable evidence indicates that angiotensin II is an intracrine. Also, general principles of intracrine functionality have been developed. Thus, recent evidence demonstrates that the prorenin/renin molecule is an intracrine enzyme. Here, the actions of intracrine enzymes (angiogenin, phosphoglucose isomerase, phospholipase A2, granzyme A and B, thioredoxin, platelet-derived endothelial growth factor, and serine protease inhibitors) are reviewed. The relation of prorenin/renin to other intracrine enzymes, and to intracrines in general, is discussed.
Re
Richard N
RN
Research Division, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA. rre@ochsner.org
D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D004792:Enzyme Precursors / Q000502:physiology; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D012083:Renin / Q000502:physiology*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism
D004792:Enzyme Precursors; D015842:Serine Proteinase Inhibitors; D013879:Thioredoxins; D013939:Thymidine Phosphorylase; D010741:Phospholipases A; D054467:Phospholipases A2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D012697:Serine Endopeptidases; D012083:Renin; D005956:Glucose-6-Phosphate Isomerase