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Research
Interests of Dr. Jiang Chang
There
is accumulating evidence to suggest the occurrence of apoptosis
in human failing hearts. My research has been focused
on the role of slow cell death in heart failure. Apoptosis
is associated with the activation
of serial caspases in the proteolytic cascade after exposure
to apoptotic signals. The implicit assumption has been that
activation of the proteolytic cascade associated with caspase
leads inexorably toward apoptosis, with eventual heart failure
arising from myocyte loss.
Knowledge
about molecular mechanisms leading to heart failure is still
limited, but reduced gene
activities and modest activation of caspase 3 are hallmarks
of end-stage heart failure. My recent studies are evaluating
Rho-associated kinase, ROCK-1, as a direct substrate of caspase
3 in failing human hearts. I explored the functional implication
of enhanced ROCK-1 cleavage and found that the constitutively-active
ROCK-1, the product of caspase 3 cleavage, was also sufficient
by itself to induce caspase 3 activation and myocyte
apoptosis. Futhermore, my studies have revealed a novel auto-regulatory
loop for molecular induction of heart failure involving the
nascent caspase 3 dependent cleavage of ROCK-1 leading to
enhanced cyclical activation of caspase 3.
Representative Publications
L. Sun, J. Chang, S.R. Kirchhoff, A.A. Knowlton.
Activation of HSF and selective increase in heat shock proteins
by acute dexamethasone treatment. American Journal of Physiology
278:H1091-H1097; 2000.
J. Chang, A.A. Knowlton and J.S. Wasser. Expression of heat
shock proteins in turtle and mammal hearts: relationship to
anoxia tolerance. American Journal of Physiology 278:R209-R214;
2000.
J. Chang, A.A. Knowlton, F. Xu and J.S. Wasser. Activation
of the heat shock response: relationship to energy metabolites
A 31P NMR study in rat hearts. American Journal of Physiology
(Heart Circ Physiol) 280:H426-H433; 2001.
J. Chang, J.S. Wasser, R.N. Cornelussen and A.A. Knowlton.
Activation of heat-shock factor by stretch-activated channels
in rat hearts. Circulation 104:209-14; 2001.
J. Chang, L. Wei, T. Otani, K.A. Youker, M.L. Entman and R.J.
Schwartz. Inhibitory cardiac transcription factor, SRF-N, is
generated by caspase3 cleavage in human heart failure and attenuated
by ventricular unloading. Circulation 108:407-413; 2003.
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