RRC ID 19314
Author Shinkai Y, Sumi D, Toyama T, Kaji T, Kumagai Y.
Title Role of aquaporin 9 in cellular accumulation of arsenic and its cytotoxicity in primary mouse hepatocytes.
Journal Toxicol Appl Pharmacol
Abstract Aquaporin (AQP) 9 is a member of the aquaglyceroporin subfamily of AQPs in the transfer of water and small solutes such as glycerol and arsenite. It is well recognized that arsenic toxicity is associated with intracellular accumulation of this metalloid. In the present study, we examined the contribution of AQP9 to the uptake of inorganic arsenite, thereby increasing arsenic-induced cytotoxicity in primary mouse hepatocytes. Pretreatment with sorbitol as a competitive inhibitor of AQP9 and siRNA-mediated knockdown of AQP9 resulted in a significant decrease of arsenite uptake in the cell and its cytotoxicity. Furthermore, overexpression of AQP9 in HEK293 cells led to the enhancement of intracellular arsenic concentration, resulting in enhanced cytotoxicity after arsenite exposure. These results suggest that AQP9 is a channel to define arsenite sensitivity in primary mouse hepatocytes.
Volume 237(2)
Pages 232-6
Published 2009-6-1
DOI 10.1016/j.taap.2009.03.014
PII S0041-008X(09)00132-X
PMID 19341753
MeSH Animals Aquaporins / genetics Aquaporins / metabolism* Arsenic / chemistry Arsenic / metabolism Arsenic / toxicity Arsenites / metabolism* Arsenites / toxicity Cells, Cultured Environmental Pollutants / metabolism Environmental Pollutants / toxicity Enzyme Inhibitors / metabolism* Enzyme Inhibitors / toxicity Gene Expression Regulation Hepatocytes / cytology Hepatocytes / metabolism* Humans Male Mice Mice, Inbred C57BL Molecular Structure Sodium Compounds / metabolism* Sodium Compounds / toxicity Sorbitol / chemistry Sorbitol / metabolism Sorbitol / toxicity
IF 3.347
Times Cited 38
WOS Category PHARMACOLOGY & PHARMACY TOXICOLOGY
Resource
Human and Animal Cells 293(RCB1637)