ABCG2 p.Gln126Lys
| ClinVar: |
c.376C>T
,
p.Gln126*
?
, association
|
| Predicted by SNAP2: | A: D (71%), C: D (66%), D: D (80%), E: D (75%), F: D (80%), G: D (80%), H: D (63%), I: D (75%), K: D (80%), L: D (80%), M: D (63%), N: D (75%), P: D (85%), R: D (85%), S: D (75%), T: D (75%), V: D (71%), W: D (85%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Reactive oxygen species derived from xanthine oxid... Biochem Pharmacol. 2015 Sep 1;97(1):89-98. doi: 10.1016/j.bcp.2015.06.021. Epub 2015 Jun 25. Ogura J, Kuwayama K, Sasaki S, Kaneko C, Koizumi T, Yabe K, Tsujimoto T, Takeno R, Takaya A, Kobayashi M, Yamaguchi H, Iseki K
Reactive oxygen species derived from xanthine oxidase interrupt dimerization of breast cancer resistance protein, resulting in suppression of uric acid excretion to the intestinal lumen.
Biochem Pharmacol. 2015 Sep 1;97(1):89-98. doi: 10.1016/j.bcp.2015.06.021. Epub 2015 Jun 25., [PMID:26119820]
Abstract [show]
The prevalence of hyperuricemia/gout increases with aging. However, the effect of aging on function for excretion of uric acid to out of the body has not been clarified. We found that ileal uric acid clearance in middle-aged rats (11-12 months) was decreased compared with that in young rats (2 months). In middle-aged rats, xanthine oxidase (XO) activity in the ileum was significantly higher than that in young rats. Inosine-induced reactive oxygen species (ROS), which are derived from XO, also decreased ileal uric acid clearance. ROS derived from XO decreased the active homodimer level of breast cancer resistance protein (BCRP), which is a uric acid efflux transporter, in the ileum. Pre-administration of allopurinol recovered the BCRP homodimer level, resulting in the recovering ileal uric acid clearance. Moreover, we investigated the effects of ROS derived from XO on BCRP homodimer level directly in Caco-2 cells using hypoxanthine. Treatment with hypoxanthine decreased BCRP homodimer level. Treatment with hypoxanthine induced mitochondrial dysfunction, suggesting that the decreasing BCRP homodimer level might be caused by mitochondrial dysfunction. In conclusion, ROS derived from XO decrease BCRP homodimer level, resulting in suppression of function for uric acid excretion to the ileal lumen. ROS derived from XO may cause the suppression of function of the ileum for the excretion of uric acid with aging. The results of our study provide a new insight into the causes of increasing hyperuricemia/gout prevalence with aging.
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No. Sentence Comment
254 BCRP mutations, such as partially functional mutation Q126K and nonfunctional mutation Q126X, markedly increase gout risk [12,13], indicating that BCRP dysfunction affects serum uric acid level.
X
ABCG2 p.Gln126Lys 26119820:254:54
status: NEW