Simultaneous overexpression of two stress proteins in rat cardiomyocytes and myogenic cells confers protection against ischemia-induced injury.
BACKGROUND
Mitochondria are known to be a major target during ischemic cardiac injury. Previous studies have shown that in rodent myogenic cells and in the hearts of transgenic mice in which the heat shock or stress protein 70 is increased, there is a marked tolerance to ischemia/reperfusion injury. Two other heat shock proteins (HSP60 and HSP10) are known to form, within the mitochondria, a chaperonin complex that is important for mitochondrial protein folding and function. We were then interested in investigating whether increased expression of these two stress proteins is able to protect myogenic cells against ischemia/reperfusion injury.


RESULTS
We generated recombinant adenoviral vectors containing HSP60, HSP10, or a combination of the two genes. These adenoviral constructs overexpress significant amounts of these stress proteins in both rat neonatal cardiomyocytes and the myogenic H9 c2 cell line. Cells infected with an adenoviral construct overexpressing both HSP60 and HSP10 were found to be protected against simulated ischemia, whereas cells infected with adenoviral constructs overexpressing only HSP60 or HSP10 alone were not rendered tolerant to simulated ischemic injury.


CONCLUSIONS
These results suggest that the simultaneous expression of these two proteins that form a chaperonin complex in the mitochondria plays an important role in the survival of myogenic cells after ischemia/reperfusion injury.
Lau
S
S
Department of Medicine, University of California at San Diego, La Jolla 92093-0618, USA.
Patnaik
N
N
Sayen
M R
MR
Mestril
R
R
D000256:Adenoviridae; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D018835:Chaperonin 10 / Q000096:biosynthesis* / Q000302:isolation & purification; D018834:Chaperonin 60 / Q000096:biosynthesis* / Q000302:isolation & purification; D005822:Genetic Vectors; D006801:Humans; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014162:Transfection
D018835:Chaperonin 10; D018834:Chaperonin 60; D011994:Recombinant Proteins; D008715:Methionine