Myotrophin/V-1 does not act as an extracellular signal to induce myocyte hypertrophy.
The myotrophin/V-1 protein was originally found to be elevated in failing heart tissues and was described as an exogenously acting hypertrophy-inducing factor. However, several studies have proposed only intracellular functions for this protein. We investigated whether this protein is an exogenously acting hypertrophy-inducing trophin or an intracellular nuclear factor of kappa B (NFkappaB) regulatory protein. In the current report, immunofluorescence and cell fractionation studies showed that myotrophin is present only in the cytoplasm and is not actively released into the extracellular environment in response to hypertrophy-inducing stimuli. Moreover, in response to ischemia/reperfusion injury, an active release of myotrophin from adult rat myocardium was not observed. Furthermore, protein synthesis studies in rat neonatal myocytes indicated that exogenous myotrophin did not induce hypertrophy. On the other hand, myotrophin stimulates the generation of NFkappaB dimers in vitro and thus regulates the NFkappaB-mediated transcription in cardiac myocytes. Taken together, these studies suggest that myotrophin is a strictly cytosolic protein that regulates the NFkappaB-mediated transcriptional process.
Knuefermann
Pascal
P
Winters Center for Heart Failure Research, Section of Cardiology in the Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Shi
Shu-Ping
SP
Chen
Peter
P
Sakata
Yashushi
Y
Baumgarten
Georg
G
Sivasubramanian
Natarajan
N
D000818:Animals; D000831:Animals, Newborn; D017089:Ankyrin Repeat; D015153:Blotting, Western; D002458:Cell Fractionation; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D006984:Hypertrophy; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology*; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000502:physiology
D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D016328:NF-kappa B; C065700:myotrophin