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New mechanistic explanation for the localization of ulcers in the rat duodenum: Role of iron and selective uptake of cysteamineстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 14 февраля 2019 г.
- Авторы: Khomenko Tetyana, Kolodney Joanna, Pinto John T., McLaren Gordon D., Deng Xiaoming, Chen Longchuan, Tolstanova Ganna, Paunovic Brankica, Krasnikov Boris F., Hoa Neil, Cooper Arthur J.L., Szabo Sandor
- Журнал: Archives of Biochemistry and Biophysics
- Том: 525
- Номер: 1
- Год издания: 2012
- Издательство: Academic Press
- Местоположение издательства: United States
- Первая страница: 60
- Последняя страница: 70
- DOI: 10.1016/j.abb.2012.05.013
- Аннотация: Cysteamine, a coenzyme A metabolite, induces duodenal ulcers in rodents. Our recent studies showed that ulcer formation was aggravated by iron overload and diminished in iron deficiency. We hypothesized that cysteamine is selectively taken up in the duodenal mucosa, where iron absorption primarily occurs, and is transported by a carrier-mediated process. Here we report that cysteamine administration in rats leads to cysteamine accumulation in the proximal duodenum, where the highest concentration of iron in the gastrointestinal tract is found. In vitro, iron loading of intestinal epithelial cells (IEC-6) accelerated reactive oxygen species (ROS) production and increased [(14)C]cysteamine uptake. [(14)C]Cysteamine uptake by isolated gastrointestinal mucosal cells and by IEC-6 was pH-dependent and inhibited by unlabeled cysteamine. The uptake of [(14)C]cysteamine by IEC-6 was Na(+)-independent, saturable, inhibited by structural analogs, H(2)-histamine receptor antagonists, and organic cation transporter (OCT) inhibitors. OCT1 mRNA was markedly expressed in the rat duodenum and in IEC-6, and transfection of IEC-6 with OCT1 siRNA decreased OCT1 mRNA expression and inhibited [(14)C]cysteamine uptake. Cysteamine-induced duodenal ulcers were decreased in OCT1/2 knockout mice. These studies provide new insights into the mechanism of cysteamine absorption and demonstrate that intracellular iron plays a critical role in cysteamine uptake and in experimental duodenal ulcerogenesis.
- Добавил в систему: Красников Борис Фёдорович