Transcription factor AP-2alpha triggers apoptosis in cardiac myocytes.
Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of unknown etiology associated with apoptosis, cardiac dilatation, progressive heart failure and increased mortality. An elevation of the transcription factor activator protein 2alpha (AP-2alpha) is involved in vertebrate embryonic development and oncogenesis. Here, we show that AP-2alpha protein is expressed in the human heart and increased in human failing myocardium with IDC. Adenovirus-mediated overexpression of human AP-2alpha triggered apoptosis and increased mRNA levels of Bcl-2 family members Bax and Bcl-x in rat cardiomyocytes. Immunohistological analysis of human myocardium revealed an increased percentage of AP-2alpha-positive nuclei in IDC and, interestingly, a colocalization of AP-2alpha-positive but not -negative cells with a caspase-cleaved fragment of poly(ADP-ribose)polymerase. We suggest AP-2alpha as a novel cardiac regulator implicated in the activation of apoptosis in IDC.
Müller
F U
FU
Institute of Pharmacology and Toxicology, University of Münster, Domagkstr. 12, Münster D-48129, Germany. mullerf@uni-muenster.de
Loser
K
K
Kleideiter
U
U
Neumann
J
J
von Wallbrunn
C
C
Dobner
T
T
Scheld
H-H
HH
Bantel
H
H
Engels
I H
IH
Schulze-Osthoff
K
K
Schmitz
W
W
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C493673:TFAP2A protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases