The Australian Biophysics Society: 1995 Meeting: Posters

Elevated DNase I Levels in Human Idiopathic Dilated Cardiomyopathy: An Indicator of Apoptosis?

Mu Yao^*, Anne Keogh⁺, Phillip Spratt⁺ and Cristobal G. dos Remedios^*, Peter C. Kießling^{*
*Muscle Research Unit, Department of Anatomy and
Histology, The University of Sydney, New South Wales 2006, and
⁺Heart and Lung Transplant Unit, St. Vincent's Hospital, Victoria
Street, Darlinghurst, New South Wales 2010, Australia.

This is the first report to determine deoxyribonuclease I (DNase I) levels in
the human myocardium and the first to demonstrate an increased DNase I level
associated with end-stage heart failure due to idiopathic dilated
cardiomyopathy (IDCM) compared to non-diseased heart samples. Left ventricular
samples were obtained following transplantation from failing hearts of 13
patients diagnosed with IDCM and from four unused donor hearts. Using a
zymogram technique, we show that the DNase I levels of the IDCM heart samples
were significantly elevated (range 0.65 - 2.75 pg DNase I/ug protein, mean +/-
S.E. of 1.69 +/- 0.22 pg/ug) compared to four non-diseased, donor heart samples
(range 0.12 - 0.35 pg/ug protein, mean +/- S.E. of 0.22 +/- 0.05 pg/ug). The
DNase I extracted from heart tissue was characterised by: (1) a co-migration
with bovine pancreatic DNase I; (2) a pH dependence consistent with DNase I;
(3) a dependence of its activity on both Ca²⁺ and Mg²⁺
and an inhibition by Zn²⁺; and (4) an inhibition of its activity in
the presence of monomeric rabbit skeletal muscle actin. The elevated DNase I
level associated with heart failure due to IDCM suggests that apoptosis may be
implicated in pathophysiology of this disorder.

*present address: Max-Planck-Institute for Medical Research, Heidelberg,
Germany}