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.


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 A1 (pDJA1). The expression of pDJA1 was found to be restricted to the heart, as opposed to skeletal muscle, liver, lung, kidney, aorta, stomach and spleen. Expression of pDJA1 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 pDJA1 follows a transmural gradient in the left ventricle, with the highest level of expression in the subendocardium. Expression of pDJA1 slightly increased during an episode of ischemia, but increased by 4-fold during the following period of reperfusion. Adenovirus-mediated transduction of pDJA1 in isolated rat neonatal cardiac myocytes decreased by 65% the rate of apoptosis induced by staurosporine.


CONCLUSIONS
Therefore, pDJA1 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.
Depre
Christophe
C
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA. deprech@umdnj.edu
Wang
Li
L
Tomlinson
James E
JE
Gaussin
Vinciane
V
Abdellatif
Maha
M
Topper
James N
JN
Vatner
Stephen F
SF
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000235:genetics; D017403:In Situ Hybridization / Q000379:methods; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D013552:Swine; D014018:Tissue Distribution; D014161:Transduction, Genetic / Q000379:methods
D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins