17beta-estradiol prevents programmed cell death in cardiac myocytes.
The cardioprotective effects of estrogens are clearly established. However, the underlying mechanisms are poorly understood. Because programmed cell death (apoptosis) probably contributes to the loss of cardiac myocytes in heart failure and because estrogens prevent apoptosis in breast cancer cells, we investigated whether the loss of cardiac myocytes by programmed cell death could be prevented by physiological doses of 17beta-estradiol. Apoptosis of cultured cardiac myocytes was induced by staurosporine. 17beta-estradiol (10 nM) had an antiapoptotic effect as determined by morphological analysis, vital staining using the Hoechst dye 33342 and terminal transferase dUTP nick-end labeling (TUNEL). As a potential mechanism for the antiapoptotic effect of 17beta-estradiol we found a reduced activity of the ICE-like protease caspase-3 in hormone-treated myocytes. Furthermore, inhibition of apoptosis by estradiol was associated with a reduced activity of NF-kappaB transcription factors, particularly p65/RelA and p50. To our knowledge, these data provide the first indication that 17beta-estradiol in physiological concentrations inhibits apoptosis in cardiac myocytes. The antiapoptotic effect of estrogens might contribute to the known cardioprotective effect of estrogens and provides a starting point for the development of future treatment options.
Pelzer
T
T
Department of Medicine, University of Würzburg, Würzburg, D-97080, Germany.
Schumann
M
M
Neumann
M
M
deJager
T
T
Stimpel
M
M
Serfling
E
E
Neyses
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D008858:Microscopy, Phase-Contrast; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000187:drug effects; D015345:Oligonucleotide Probes / Q000235:genetics; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology
D016328:NF-kappa B; D009707:Nucleosomes; D015345:Oligonucleotide Probes; D004958:Estradiol; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine