Characterization of pDJA1, a cardiac-specific chaperone found by genomic profiling of the post-ischemic swine heart

Background: Previously, we showed by subtractive hybridization in a swine model of ischemia/reperfusion that an upregulation of genes participating in mechanisms of cell survival is a potential genomic mechanism to tilt the balance from necrosis to functional reversibility. Methods and results: We present here the full-length sequencing and characterization of a novel gene that was found in this subtraction, encoding a cardiac-specific DnaJ-like co-chaperone that we call Pig DnaJ-like protein AI (pDJAl). The expression of pDJAl was found to be restricted to the heart, as opposed to skeletal muscle, liver, lung, kidney, aorta, stomach and spleen. Expression of pDJAl is restricted to cardiac myocytes, as determined by in situ hybridization. The transcript is expressed more in the left ventricle than in the other cardiac chambers. Remarkably, expression of pDJAl follows a transmural gradient in the left ventricle, with the highest level of expression in the subendocardium. Expression of pDJAl slightly increased during an episode of ischemia, but increased by 4-fold during the following period of reperfusion. Adenovirus-mediated transduction of pDJAl in isolated rat neonatal cardiac myocytes decreased by 65% the rate of apoptosis induced by staurosporine. Conclusion: Therefore, pDJAl is a novel heart-specific, ventricle-enriched cardioprotective co-chaperone, which participates in the program of cell survival that limits irreversible damage in post-ischemic myocardium. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.