Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
This study examined how the 1199G > A polymorphism in the
ABCB1
gene encoding
P-glycoprotein
(
P-gp
) affects the protein's expression, ATPase activity, and ability to pump female steroid sex hormones out of LLC-PK1 cells. The
ABCB1
(1199G) or
ABCB1
(1199A) allele was transfected into cells, which were incubated for 48 h with various hormone concentrations, then analyzed by Western blotting to examine expression of
P-gp
protein and by reverse transcription-polymerase chain reaction (RT-PCR) to examine expression of mRNA. Cells were also compared in terms of their transepithelial permeability to steroid sex hormones in the presence and absence of the specific
P-gp
inhibitor GF120918.
P-gp
ATPase activity induced by steroid sex hormones was also assayed.
Estriol
and ethynyl estradiol up-regulated levels of
ABCB1
mRNA in a concentration-dependent manner, with
ABCB1
(1199A) mRNA showing greater up-regulation than
ABCB1
(1199G) mRNA. Estrone, estriol, and ethynyl estradiol were substrates of both types of
P-gp
in transepithelial permeability assays, and the
ABCB1
(1199A) protein showed a significantly higher net efflux ratio for estrone (13.4
vs.
7.4,
p
< 0.005), estriol (5.6
vs.
3.3,
p
< 0.05), and ethynyl estradiol (12.7
vs.
5.3,
p
< 0.005). Induction of
P-gp
ATPase activity by ethynyl estradiol and progesterone increased with increasing hormone concentration, and the magnitude of stimulation was greater for
ABCB1
(1199A)
P-gp
than for
ABCB1
(1199G)
P-gp
. These results indicate that the
ABCB1
(1199G > A) polymorphism influences steroid sex hormone-induced expression and function of
P-gp
, which may help to explain inter-patient differences in
P-gp
-mediated chemotherapy resistance
in vivo
.
...
PMID:Effects of the
ABCB1
(1199G > A) Polymorphism on Steroid Sex Hormone-Induced P-Glycoprotein Expression, ATPase Activity, and Hormone Efflux. 2908 97
