Expression of Id1 results in apoptosis of cardiac myocytes through a redox-dependent mechanism.
We have constructed a recombinant adenovirus (Ad.Id1) that allows for efficient expression of the helix-loop-helix protein Id1. After infection with Ad.Id1, neonatal cardiac myocytes display a significant reduction in viability, which was proportional to the level of Id1 expression. A similar effect was observed in adult myocytes. Morphological and biochemical assays demonstrated that Id1 expression resulted in myocyte apoptosis. In contrast, expression of Id1 in endothelial cells, vascular smooth muscle cells, or fibroblasts did not affect the viability of these cells. Along with the induction of apoptosis, the expression of Id1 in neonatal cardiac myocytes resulted in an increase in the level of intracellular reactive oxygen species. The source of these reactive oxygen species appears to be the mitochondria. Reducing the ambient oxygen concentration or treatment with a cell-permeant H2O2 scavenger prevented Id1-stimulated apoptosis in cardiac myocytes. These results suggest that the expression of Id1 leads to the induction of apoptosis in cardiac myocytes through a redox-dependent mechanism.
Tanaka
K
K
Cardiology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pracyk
J B
JB
Takeda
K
K
Yu
Z X
ZX
Ferrans
V J
VJ
Deshpande
S S
SS
Ozaki
M
M
Hwang
P M
PM
Lowenstein
C J
CJ
Irani
K
K
Finkel
T
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000032:analysis; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000502:physiology*
D016166:Free Radical Scavengers; C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D014157:Transcription Factors; D018995:Myosin Heavy Chains; D010100:Oxygen