Abstract |
Aquaporins (AQP) conduct small, uncharged molecules, such as water (orthodox AQPs), ammonia (aquaammoniaporins) or glycerol ( aquaglyceroporins). The physiological functions of AQPs are involved in osmotic volume regulation or the transport of biochemical precursors and metabolic waste products. The recent identification of hydrogen peroxide (H₂O₂) as a permeant of certain AQPs suggests additional roles in mitigating oxidative stress or enabling paracrine H₂O₂ signalling. Yet, an analysis of the structural requirements of the H₂O₂ permeability of AQPs is missing. We subjected a representative set of wild-type and mutant AQPs to a newly established quantitative phenotypic assay. We confirmed high H₂O₂ permeability of the human aquaammoniaporin AQP8 and found intermediate H₂O₂ permeability of the prototypical orthodox water channel AQP1 from the rat. Differences from an earlier report showing an absence of H₂O₂ permeability of human AQP1 can be explained by expression levels. By generating point mutations in the selectivity filter of rat orthodox aquaporin AQP1, we established a correlation of H₂O₂ permeability primarily with water permeability and secondarily with the pore diameter. Even the narrowest pore of the test set (i.e. rat orthodox aquaporin AQP1 H180F with a pore diameter smaller than that of natural orthodox AQPs) conducted water and H₂O₂. We further found that H₂O₂ permeability of the aquaglyceroporin from the malaria parasite Plasmodium falciparum was lower despite its wider pore diameter. The data suggest that all water-permeable AQPs are H₂O₂ channels, yet H₂O₂ permeability varies with the isoform. Thus, generally, AQPs must be considered as putative players in situations of oxidative stress (e.g. in Plasmodium-infected red blood cells, immune cells, the cardiovascular system or cells expressing AQP8 in their mitochondria).
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Authors | Abdulnasser Almasalmeh, Dawid Krenc, Binghua Wu, Eric Beitz |
Journal | The FEBS journal
(FEBS J)
Vol. 281
Issue 3
Pg. 647-56
(Feb 2014)
ISSN: 1742-4658 [Electronic] England |
PMID | 24286224
(Publication Type: Comparative Study, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 FEBS. |
Chemical References |
- Aqp1 protein, rat
- Aquaporins
- Mutant Proteins
- PfAQP protein, Plasmodium falciparum
- Porins
- Protein Isoforms
- Protozoan Proteins
- Recombinant Proteins
- aquaporin 8
- Water
- Aquaporin 1
- Hydrogen Peroxide
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Topics |
- Amino Acid Substitution
- Animals
- Aquaporin 1
(chemistry, genetics, metabolism)
- Aquaporins
(chemistry, genetics, metabolism)
- Cell Membrane Permeability
- Humans
- Hydrogen Peroxide
(metabolism)
- Kinetics
- Mutant Proteins
(chemistry, metabolism)
- Oxidative Stress
- Plasmodium falciparum
(metabolism)
- Point Mutation
- Porins
(chemistry, genetics, metabolism)
- Protein Conformation
- Protein Isoforms
- Protoplasts
(metabolism)
- Protozoan Proteins
(chemistry, genetics, metabolism)
- Rats
- Recombinant Proteins
(chemistry, genetics, metabolism)
- Water
(metabolism)
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