Premium
17β‐Estradiol inhibition of NADPH oxidase expression in human endothelial cells
Author(s) -
Wagner Andreas H.,
Schroeter Marco R.,
Hecker Markus
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0123com
Subject(s) - nadph oxidase , chemistry , umbilical vein , nitric oxide , superoxide , nitric oxide synthase , biochemistry , reactive oxygen species , enzyme , in vitro , organic chemistry
We investigated the hypothesis that the antiatherosclerotic effect of 17β‐estradiol (E 2 ) is due to a shift in the nitric oxide (NO)/superoxide (O 2 - ) balance in the vessel wall, thereby increasing the bio‐availability of NO. In human umbilical vein cultured endothelial cells, E 2 (1–100 nmol/l), but not 17α‐estradiol, caused a time‐ and concentration‐dependent decrease in expression of the NADPH oxidase subunit gp91phox (up to 60% inhibition at both the mRNA and protein level). This effect was prevented by coincuba‐tion with the estrogen receptor antagonists tamoxifen and ICI 182,780 (1 μmol/1 each). Within the same concentration range, E 2 also up‐regulated endothelial nitric oxide synthase expression (~two fold). Moreover, preincubation of the cells with E 2 or a gp91phox antisense oligonucleotide significantly decreased their capacity to generate O 2 - on phorbol ester stimulation (i.e., assembly of the active NADPH oxidase complex). Blockade of NO synthase activity, on the other hand, had no effect on phorbol ester‐stimulated O 2 - formation. In addition, E 2 (100 nmol/l) inhibited the increase in adhesion molecule and chemokine expression in cells exposed to cyclic strain. Cyclic strain enhanced endothelial O 2 - formation, thereby offsetting the inhibitory effect of NO on the expression of these gene products. E 2 thus seems to act as an antioxidant at the genomic level which by improving the NO/O 2 - balance normalizes expression of proatherosclerotic gene products in endothelial cells.—Wagner, A. H., Schroeter, M. R., Hecker, M. 17β‐Estradiol inhibition of NADPH oxidase expression in human endothelial cells. FASEB J. 15, 2121–2130 (2001)