Holcocrinus, a new inadunate crinoid genus from the lower Mississippian [Upper Mississippi Valley]

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ID: 299151
1945
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Abstract
Hundreds of millions of people world-wide are exposed to unacceptable levels of arsenic in drinking water. This is a public health crisis because arsenic is a Group I (proven) human carcinogen. Human cells methylate arsenic to monomethylarsonous acid (MMAIII), monomethylarsonic acid (MMAV), dimethylarsinous acid (DMAIII), and dimethylarsinic acid (DMAV). Although the liver is the predominant site for arsenic methylation, elimination occurs mostly in urine. The protein(s) responsible for transport of arsenic from the liver (into blood), ultimately for urinary elimination are unknown. Human multidrug resistance protein 1 (MRP1/ABCC1) and MRP2 (ABCC2), are established arsenic efflux pumps, but unlike the related MRP4 (ABCC4), are not present at the basolateral membrane of hepatocytes. MRP4 is also found at the apical membrane of renal proximal tubule cells making it an ideal candidate for urinary arsenic elimination. In the current study, human MRP4 expressed in HEK293 cells reduced the cytotoxicity and cellular accumulation of AsV, MMAIII, MMAV, DMAIII, and DMAV while two other hepatic basolateral MRPs (MRP3 and MRP5) did not. Transport studies with MRP4-enriched membrane vesicles revealed that the diglutathione conjugate of MMAIII [MMA(GS)2] and DMAV were the transported species. MMA(GS)2 and DMAV transport was osmotically sensitive, allosteric (Hill coefficients of 1.4 ± 0.2 and 2.9 ± 1.2, respectively), and high affinity (K0.5 of 0.70 ± 0.16 μM and 0.22 ± 0.15 μM, respectively). DMAV transport was pH dependent with highest affinity and capacity at pH 5.5. These results suggest human MRP4 could be a major player in the elimination of arsenic.
Reference Key
openalex_W2049735769 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Esben Kirk
Journal american journal of science
Year 1945
DOI
10.2475/ajs.243.9.517
URL
https://doi.org/10.2475/ajs.243.9.517
Keywords Keywords not found

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