Role of aquaporin 9 in cellular accumulation of arsenic and its cytotoxicity in primary mouse hepatocytes

Yasuhiro Shinkai, Daigo Sumi, Takashi Toyama, Toshiyuki Kaji, Yoshito Kumagai

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)232-236
Number of pages5
JournalToxicology and Applied Pharmacology
Volume237
Issue number2
DOIs
Publication statusPublished - 2009 Jun 1
Externally publishedYes

Keywords

  • Aquaporin 9
  • Cytotoxicity
  • Inorganic arsenite
  • Sorbitol

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Role of aquaporin 9 in cellular accumulation of arsenic and its cytotoxicity in primary mouse hepatocytes'. Together they form a unique fingerprint.

  • Cite this