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

Jennifer M. Carbrey, Linhua Song, Yao Zhou, Masafumi Yoshinaga, Aleksandra Rojek, Yiding Wang, Yangjian Liu, Heidi L. Lujan, Stephen E. DiCarlo, Søren Nielsen, Barry P. Rosen, Peter C Agre, Rita Mukhopadhyay

Research output: Contribution to journalArticle

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 NaAsO2, AQP9-null mice suffer reduced survival rates (LD50, 12 mg/kg) compared with WT mice (LD50, 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 NaAsO2 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 ≈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.

Original languageEnglish (US)
Pages (from-to)15956-15960
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number37
DOIs
StatePublished - Sep 15 2009

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Aquaglyceroporins
Arsenic
Liver
Lethal Dose 50
Injections
Bradycardia

ASJC Scopus subject areas

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Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice. / Carbrey, Jennifer M.; Song, Linhua; Zhou, Yao; Yoshinaga, Masafumi; Rojek, Aleksandra; Wang, Yiding; Liu, Yangjian; Lujan, Heidi L.; DiCarlo, Stephen E.; Nielsen, Søren; Rosen, Barry P.; Agre, Peter C; Mukhopadhyay, Rita.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 37, 15.09.2009, p. 15956-15960.

Research output: Contribution to journalArticle

Carbrey, JM, Song, L, Zhou, Y, Yoshinaga, M, Rojek, A, Wang, Y, Liu, Y, Lujan, HL, DiCarlo, SE, Nielsen, S, Rosen, BP, Agre, PC & Mukhopadhyay, R 2009, 'Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 37, pp. 15956-15960. https://doi.org/10.1073/pnas.0908108106
Carbrey, Jennifer M. ; Song, Linhua ; Zhou, Yao ; Yoshinaga, Masafumi ; Rojek, Aleksandra ; Wang, Yiding ; Liu, Yangjian ; Lujan, Heidi L. ; DiCarlo, Stephen E. ; Nielsen, Søren ; Rosen, Barry P. ; Agre, Peter C ; Mukhopadhyay, Rita. / Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 37. pp. 15956-15960.
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