TY - JOUR
T1 - Akt plays a central role in the anti-apoptotic effect of estrogen in endothelial cells
AU - Koga, Miho
AU - Hirano, Katsuya
AU - Hirano, Mayumi
AU - Nishimura, Junji
AU - Nakano, Hitoo
AU - Kanaide, Hideo
N1 - Funding Information:
We thank Mr. Brian Quinn for linguistic comments and help with the manuscript. This study was supported in part by the grant from the 21st Century COE Program and Grants-in-Aid for Scientific Research (No. 15590758) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2004/11/5
Y1 - 2004/11/5
N2 - Estrogen has been reported to inhibit apoptosis in vascular endothelial cells. However, its precise mechanism still remains to be elucidated. Here we determined the role of Akt in the anti-apoptotic effect of estrogen. 17β-Estradiol prevented the apoptosis induced by TNF-α in bovine aortic endothelial cells, as evaluated by double staining with fluorescein isothiocyanate-conjugated annexin V and propidium iodide. Introducing a dominant negative mutant of Akt by using a cell-penetrating peptide of Tat protein inhibited the anti-apoptotic effect of estrogen in a concentration-dependent manner, and resulted in the complete inhibition of the anti-apoptotic effect of 17β-estradiol at 1 nM and higher concentrations. The dominant negative mutant without the cell-penetrating peptide and Tat peptide-conjugated protein A had no effect. The intracellular protein transduction was confirmed by immunoblot analysis. Our observations thus provide first direct evidence that Akt plays a central role in the anti-apoptotic effect of estrogen in vascular endothelial cells.
AB - Estrogen has been reported to inhibit apoptosis in vascular endothelial cells. However, its precise mechanism still remains to be elucidated. Here we determined the role of Akt in the anti-apoptotic effect of estrogen. 17β-Estradiol prevented the apoptosis induced by TNF-α in bovine aortic endothelial cells, as evaluated by double staining with fluorescein isothiocyanate-conjugated annexin V and propidium iodide. Introducing a dominant negative mutant of Akt by using a cell-penetrating peptide of Tat protein inhibited the anti-apoptotic effect of estrogen in a concentration-dependent manner, and resulted in the complete inhibition of the anti-apoptotic effect of 17β-estradiol at 1 nM and higher concentrations. The dominant negative mutant without the cell-penetrating peptide and Tat peptide-conjugated protein A had no effect. The intracellular protein transduction was confirmed by immunoblot analysis. Our observations thus provide first direct evidence that Akt plays a central role in the anti-apoptotic effect of estrogen in vascular endothelial cells.
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U2 - 10.1016/j.bbrc.2004.09.060
DO - 10.1016/j.bbrc.2004.09.060
M3 - Article
C2 - 15465021
AN - SCOPUS:4744348896
VL - 324
SP - 321
EP - 325
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -