The G671V variant of MRP1/ABCC1 links doxorubicin-induced acute cardiac toxicity to disposition of the glutathione conjugate of 4-hydroxy-2-trans-nonenal.
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| Abstract | :
Doxorubicin-induced acute cardiotoxicity is associated with the Gly671Val (G671V; rs45511401) variant of multidrug resistance-associated protein 1 (MRP1). Doxorubicin redox cycling causes lipid peroxidation and generation of the reactive electrophile, 4-hydroxy-2-trans-nonenal (HNE). Glutathione forms conjugates with HNE, yielding an MRP1 substrate, GS-HNE, whose intracellular accumulation can cause toxicity. |
| Year of Publication | :
2012
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| Journal | :
Pharmacogenetics and genomics
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| Volume | :
22
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| Issue | :
4
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| Number of Pages | :
273-84
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| ISSN Number | :
1744-6872
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| URL | :
https://doi.org/10.1097/FPC.0b013e328350e270
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| DOI | :
10.1097/FPC.0b013e328350e270
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| Short Title | :
Pharmacogenet Genomics
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