Mechanisms of arsenic toxicity and transport in microorganisms

Arsenic is an ubiquitous element present in the environment either through geological or anthropogenic activities. Millions of people all over the world are exposed to arsenic mainly via air, drinking water and food sources, which results in higher incidence of cancer. Several mechanisms by which arsenic compounds induce tumorigenesis have been proposed. Arsenic mediates its toxicity by generating oxidative stress, inducing protein misfolding, promoting genotoxicity, hampering DNA repair and disrupting signal transduction. Thus, all organisms have developed multiple pathways for arsenic detoxification. In this article, we review recent advances in the understanding of arsenic toxicity and its transport routes in prokaryotes and eukaryotes, including a dual role of aquaglyceroporins in the uptake and efflux, active transport out of the cell via secondary ion pumps and sequestration of metalloid-thiol conjugates into vacuoles by primary ABC transporters. We believe that such studies are of high importance due to the increasing usage of arsenic-based drugs in the treatment of certain types of cancer and diseases caused by protozoan parasites as well as for the development of bio-and phytoremediation strategies for metalloid-polluted areas. 1. Introduction. 2. The chemical properties and the presence of arsenic in the environment. 3. Pathways for arsenic uptake. 4. Mechanism of trivalent arsenic toxicity. 4.1. Oxidative stress. 4.2. Arsenic binding to proteins. 4.3. Protein aggregation. 5. Pentavalent arsenic toxicity. 6. Cellular detoxification mechanisms of arsenic compounds. 6.1. ars operons. 6.2. ACR genes. 6.3. Removal of arsenic conjugates by the ABC transporters. 6.4. Bi-directional transport of arsenic. 7. Summary 1. Wstęp. 2. Właściwości chemiczne i występowanie arsenu w środowisku. 3. Sposoby wnikania arsenu do komórek. 4. Mechanizmy toksycznego działania arsenu trójwartościowego. 4.1. Stres oksydacyjny. 4.2. Wiązanie z białkami. 4.3. Agregacja białek. 5. Toksyczność pięciowartościowego arsenu. 6. Mechanizmy detoksykacji komórek ze związków arsenu. 6.1. Operony ars . 6.2. Geny ACR . 6.3. Usuwanie koniugatów arsenu przez pierwotne transportery ABC. 6.4. Dwukierunkowy transport arsenu. 7. Podsumowanie