HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway

• Published in: American journal of physiology. Heart and circulatory physiology 2007-06, Vol.292 (6), p.H3052-H3056
• Main Authors: Gupta, Sanjiv, Knowlton, A. A
• Format: Article
• Language: English
• Subjects: Amiloride - analogs & derivatives; Amiloride - pharmacology; Animals; beta-Cyclodextrins - pharmacology; Biochemistry; Brefeldin A - pharmacology; Cardiology; Cardiovascular system; Caveolin 1 - metabolism; Cell Hypoxia; Chaperonin 60 - metabolism; Golgi Apparatus - metabolism; HSC70 Heat-Shock Proteins - metabolism; HSP90 Heat-Shock Proteins - metabolism; Male; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Plasma; Protein Transport; Proteins; Rats; Rats, Sprague-Dawley; Secretory Vesicles - drug effects; Secretory Vesicles - metabolism; Subcellular Fractions - metabolism
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01355.2006

Molecular and Cellular Cardiology, Cardiovascular Division, University of California, Davis; and Sacramento Veterans Affairs Medical Center, Sacramento, California Submitted 12 December 2006 ; accepted in final form 12 February 2007 The heat shock proteins (HSP) are a highly conserved family of proteins with critical functions in protein folding, protein trafficking, and cell signaling. These proteins also protect the cell against injury. HSP60 has been found in the extracellular space and has been identified in the plasma of some individuals. HSP60 is thought to be a "danger signal" to the immune system and is also highly immunogenic. Thus extracellular HSP60 is possibly toxic to the cell. The mechanism by which HSP60 is released into the extracellular space is unknown, as is whether it is released by cardiac myocytes. We investigated several different pathways controlling protein release including the classic, Golgi-mediated pathway. We found that HSP60 is released via exosomes, and that within the exosome, HSP60 is tightly attached to the exosome membrane. heat shock protein; toll-like receptor; protein secretion Address for reprint requests and other correspondence: A. A. Knowlton, Molecular & Cellular Cardiology, Division of Cardiovascular Medicine, Univ. of California, Davis, One Shields Ave., Davis, CA 95616 (e-mail: aaknowlton{at}ucdavis.edu )