期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 99, 期 9, 页码 6053-6058出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.092131899
关键词
fps1p; GlpF; acute promyelocytic leukemia
资金
- NEI NIH HHS [R01 EY011239, EY11239] Funding Source: Medline
- NHLBI NIH HHS [R37 HL048268, R01 HL033991, R01 HL048268, HL48268, HL33991] Funding Source: Medline
- NIDDK NIH HHS [T32 DK007712, T32 DK7712-08] Funding Source: Medline
- NIEHS NIH HHS [ES10344, P42 ES010344] Funding Source: Medline
- NIGMS NIH HHS [GM55425, R01 GM055425, R37 GM055425] Funding Source: Medline
Much is known about the transport of arsenite and antimonite into microbes, but the identities of mammalian transport proteins are unknown. The Saccharomyces cerevisiae FPS1 gene encodes a membrane protein homologous to the bacterial aquaglyceroporin GlpF and to mammalian aquaglyceroporins AQP7 and AQP9. Fps1p mediates glycerol uptake and glycerol efflux in response to hypoosmotic shock. Fps1p has been shown to facilitate uptake of the metalloids arsenite and antimonite, and the Escherichia coli homolog, GlpF, facilitates the uptake and sensitivity to metalloid salts. In this study, the ability of mammalian aquaglyceroporins AQP7 and AQP9 to substitute for the yeast Fps1p was examined. The fps1Delta strain of S. cerevisiae exhibits increased tolerance to arsenite and antimonite compared to a wild-type strain. introduction of a plasmid containing AQP9 reverses the metalloid tolerance of the deletion strain. AQP7 was not expressed in yeast. The fps1Delta cells exhibit reduced transport of As-73(III) or Sb-125(III), but uptake is enhanced by expression of AQP9. Xenopus laevis oocytes microinjected with either AQP7 or AQP9 cRNA exhibited increased transport of As-73(III). These results suggest that AQP9 and AQP7 may be a major routes of arsenite uptake into mammalian cells, an observation potentially of large importance for understanding the action of arsenite as a human toxin and carcinogen, as well as its efficacy as a chemotherapeutic agent for acute promyelocytic leukemia.
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