کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2511905 1118299 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
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
ترجمه فارسی عنوان
گونه های فعال اکسیژن مشتق شده از اکسیداز زانتین اکسیداز قطع پروتئین مقاومت پروتئینی مقاومت به سرطان سینه، منجر به سرکوب اسید اوریک اسید به روده
کلمات کلیدی
هیپریریسمی، سالخورده، گونه های اکسیژن واکنش پذیر، پروتئین مقاوم به سرطان پستان، دفع اسید اوریک
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
چکیده انگلیسی

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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 97, Issue 1, 1 September 2015, Pages 89–98
نویسندگان
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