Elevated DNase I levels in human idiopathic dilated cardiomyopathy: an indicator of apoptosis?
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/microgram protein, mean +/- S.E. of 1.69 +/- 0.22 pg/micrograms) compared to four non-diseased, donor heart samples (range 0.12-0.35 pg/microgram protein, mean +/- S.E. of 0.22 +/- 0.05 pg/microgram). The DNase I extracted from heart tissue was characterized 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 levels associated with heart failure due to IDCM suggests that apoptosis may be implicated in pathophysiology of this disorder.
Yao
M
M
Department of Anatomy and Histology, University of Sydney, New South Wales, Australia.
Keogh
A
A
Spratt
P
P
dos Remedios
C G
CG
Kiessling
P C
PC
D000199:Actins / Q000494:pharmacology; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology*; D003850:Deoxyribonuclease I / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D012016:Reference Values; D012727:Sex Characteristics
D000199:Actins; D015415:Biomarkers; D003850:Deoxyribonuclease I