Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

Show full item record

Title: Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice
Author: Mukhopadhyay, R; Agre, P; Rosen, B P; Nielsen, S; DiCarlo, S E; Lujan, H L; Liu, Y; Wang, Y; Rojek, A; Yoshinaga, M; Zhou, Y; Song, L; Carbrey, J M
Abstract: Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO(2), AQP9-null mice suffer reduced survival rates (LD(50), 12 mg/kg) compared with WT mice (LD(50), 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10-20 times more arsenic than WT mice. Within hours after NaAsO(2) injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only approximately 10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.
Date: 2009-09-15
Citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15956-60. Epub 2009 Sep 8.
Subject: Arsenic/toxicity

Files in this item

Files Size Format Download
PNAS-2009-Carbrey-15956-60.pdf 881.9Kb application/pdf Download

The following license files are associated with this item:

This item appears in the following Collection(s)

Show full item record