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B crystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion
* Cardiovascular Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030-1110, USA; and
Department of Medicine, University of California at San Diego, San Diego, California, USA
1Correspondence: Cardiovascular Division, Department of Surgery, 263 Farmington Ave., Farmington, CT 06030-1110, USA. E-mail : ddas{at}neuron.uchc.edu
We investigated whether enhanced expression of 
B crystallin, a
stress-inducible molecular chaperone of the small heat shock family,
can protect myocardial contractile apparatus against ischemia
reperfusion (I/R) injury. Transgenic mice overexpressing B
crystallin were generated using the 0.76 kb rat B crystallin cDNA
cloned into a pCAGGS plasmid driven by a human cytomegalovirus
expression system. Southern analysis confirmed transgene integration
and Northern and Western blotting characterized expression (3.1-fold
and 6.9-fold elevations in myocardial mRNA and protein levels,
respectively). Extent of functional recovery over a 3 h
reperfusion period following a 20 min ischemic period in transgenic and
wild-type mouse hearts was assessed using an ex vivo
work-performing heart preparation. The transgenic group displayed
significantly higher values of DP at R45 min (29.14±1.9 mm Hg vs.
17.6±0.7 mm Hg), R60 min (31.56±1.7 mm Hg vs. 17.8±0.8 mm Hg), and
R75 min (32.5±2.2 mm Hg vs. 16.9±0.9 mm Hg), and of dLVP/dt at R45
min (1740.2±111.5 mm Hg.s-1 vs. 548.7±82.2 mm
Hg.s-1) and R60 min (1199.8±104.6 mm Hg.s-1
vs. 466.9±61.1 mm Hg.s-1). The transgenic group also
displayed development of less oxidative stress, decreased extent of
infarction, and attenuated cardiomyocyte apoptotic cell death.
Transgene overexpression of B crystallin was therefore successful in
diminishing the independent contributory effects of both necrosis and
apoptosis on I/R-induced cell death.—Ray, P. S., Martin, J. L., Swanson, E. A., Otani, H., Dillmann, W. H., Das, D. K. Transgene overexpression of B crystallin confers simultaneous
protection against cardiomyocyte apoptosis and necrosis during
myocardial ischemia and reperfusion.
Key Words: B crystallin • transgenic • ischemia/reperfusion • oxidative stress
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