Significance of downregulation of renal organic cation transporter (SLC47A1) in cisplatin-induced proximal tubular injury

To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs) influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1) in tubular cells. To detect ch...

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Published in:OncoTargets and therapy 2015-01, Vol.8, p.1701-1706
Main Authors: Mizuno, Tomohiro, Sato, Waichi, Ishikawa, Kazuhiro, Terao, Yuki, Takahashi, Kazuo, Noda, Yukihiro, Yuzawa, Yukio, Nagamatsu, Tadashi
Format: Article
Language:English
Subjects:
Advanced glycation end products
Diabetes
Health aspects
Injuries
Ion transport
Kidneys
Original Research
Physiological aspects
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Summary:To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs) influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1) in tubular cells. To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S86743