The Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity
Abstract The metabolic biotransformation of xenobiotics to chemically reactive metabolites can, in some instances, underlie the pathogenesis of certain adverse drug reactions, due to the development of chemical or oxidative stress. In order to guard against such stresses, mammalian cells have evolve...
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| Veröffentlicht in: | Toxicology (Amsterdam) 2008-04, Vol.246 (1), p.24-33 |
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| container_title | Toxicology (Amsterdam) |
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| creator | Copple, Ian M Goldring, Christopher E Kitteringham, Neil R Park, B. Kevin |
| description | Abstract The metabolic biotransformation of xenobiotics to chemically reactive metabolites can, in some instances, underlie the pathogenesis of certain adverse drug reactions, due to the development of chemical or oxidative stress. In order to guard against such stresses, mammalian cells have evolved multi-faceted, highly-regulated defence systems, one of the most important being that which is regulated by the transcription factor Nrf2. Through regulating the expression of numerous cytoprotective genes, Nrf2 serves as a critical determinant of a cell's capacity to survive, or succumb, to a toxic insult. The aim of this review is to summarise our current understanding of the biochemistry that underlies the Nrf2 defence pathway, and highlight the important role of this transcription factor in the protection against drug-induced toxicity, primarily through the examination of recent investigations that have demonstrated an increased vulnerability to various toxins in animals lacking Nrf2. |
| doi_str_mv | 10.1016/j.tox.2007.10.029 |
| format | Article |
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Kevin</creatorcontrib><title>The Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Abstract The metabolic biotransformation of xenobiotics to chemically reactive metabolites can, in some instances, underlie the pathogenesis of certain adverse drug reactions, due to the development of chemical or oxidative stress. In order to guard against such stresses, mammalian cells have evolved multi-faceted, highly-regulated defence systems, one of the most important being that which is regulated by the transcription factor Nrf2. Through regulating the expression of numerous cytoprotective genes, Nrf2 serves as a critical determinant of a cell's capacity to survive, or succumb, to a toxic insult. The aim of this review is to summarise our current understanding of the biochemistry that underlies the Nrf2 defence pathway, and highlight the important role of this transcription factor in the protection against drug-induced toxicity, primarily through the examination of recent investigations that have demonstrated an increased vulnerability to various toxins in animals lacking Nrf2.</description><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adaptor Proteins, Signal Transducing - physiology</subject><subject>Animals</subject><subject>Cell defence</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Cytoskeletal Proteins - physiology</subject><subject>Drug-induced toxicity</subject><subject>Emergency</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Intracellular Signaling Peptides and Proteins - physiology</subject><subject>Keap1</subject><subject>Kelch-Like ECH-Associated Protein 1</subject><subject>Mice</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NF-E2-Related Factor 2 - physiology</subject><subject>Nrf2</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Signal Transduction - physiology</subject><subject>Xenobiotics - antagonists & inhibitors</subject><subject>Xenobiotics - toxicity</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd9qFDEUxkNR7Fp9gN5Irryb9SSZZJIKQin-w6JQK3gX0uRMm3V2ZpvMqHvnO_QNfRIz7ELBi14lJ3zfx5ffIeSYwZIBU69Wy3H4veQATZmXwM0BWTDdmEowLR-RBQiAqtbi-yF5mvMKALio1RNyyDRowbVYkIvLG6SfU8v__rn7hG7DaMAWe49048abX257Qi-GDmns6SYNI_oxDj111y72eaQhTddV7MPkMdDSJfo4bp-Rx63rMj7fn0fk27u3l2cfqvMv7z-enZ5XXkg-VtywWgoltaxBmLatQ8tUrYwSpkFlpEGhTNMWbZmbwJS8EiB149EY5TgTR-TlLrcUu50wj3Yds8eucz0OU7YclDRKz0K2E_o05JywtZsU1y5tLQM7g7QrW8rbGeT8VEAWz4t9-HS1xnDv2JMrgtc7AZYv_oyYbPZxBhdiKpRsGOKD8W_-c_su9tG77gduMa-GKfWFnWU2cwv267zJeZHQlBBZbv8AR1aXjw</recordid><startdate>20080403</startdate><enddate>20080403</enddate><creator>Copple, Ian M</creator><creator>Goldring, Christopher E</creator><creator>Kitteringham, Neil R</creator><creator>Park, B. 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Through regulating the expression of numerous cytoprotective genes, Nrf2 serves as a critical determinant of a cell's capacity to survive, or succumb, to a toxic insult. The aim of this review is to summarise our current understanding of the biochemistry that underlies the Nrf2 defence pathway, and highlight the important role of this transcription factor in the protection against drug-induced toxicity, primarily through the examination of recent investigations that have demonstrated an increased vulnerability to various toxins in animals lacking Nrf2.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18083283</pmid><doi>10.1016/j.tox.2007.10.029</doi><tpages>10</tpages></addata></record> |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adaptor Proteins, Signal Transducing - metabolism Adaptor Proteins, Signal Transducing - physiology Animals Cell defence Cytoskeletal Proteins - metabolism Cytoskeletal Proteins - physiology Drug-induced toxicity Emergency Gene Expression Regulation, Enzymologic Humans Intracellular Signaling Peptides and Proteins - metabolism Intracellular Signaling Peptides and Proteins - physiology Keap1 Kelch-Like ECH-Associated Protein 1 Mice NF-E2-Related Factor 2 - metabolism NF-E2-Related Factor 2 - physiology Nrf2 Oxidative Stress - drug effects Oxidative Stress - physiology Signal Transduction - physiology Xenobiotics - antagonists & inhibitors Xenobiotics - toxicity |
| title | The Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity |
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