Abstract
The ATP Binding Cassette B1 (ABCB1) transporter has critical roles in endo- and xenobiotic efficacy and toxicity. To understand population variability in hepatic transport we determined ABCB1 mRNA and protein levels in total liver lysates sampled from 8 pre-defined sites (n = 24, 18–69 years), and in S9 from randomly acquired samples (n = 87, 7 days–87 years). ABCB1 levels did not differ significantly throughout individual livers and showed 4.4-fold protein variation between subjects. Neither mRNA nor protein levels varied with sex, ethnicity, obesity or triglycerides in lysates or S9 (that showed the same relationships), but protein levels were lower in pediatric S9 (p < 0.0001), with 76% of adult ABCB1 present at birth and predicted to mature in 5 years. Pediatric total liver lysates were not available. In summary, opportunistic collection for studying human hepatic ABCB1 is acceptable. Additionally, ABCB1 may be lower in children, indicating differential potential for toxicity and response to therapy in this special population.
Highlights
Interest in active transporters, such as the ATP Binding Cassette (ABC) proteins, has peaked in recent years because they play crucial roles in drug, chemical, hormone, and nutrient disposition [1].Clinical and environmental studies increasingly consider the effects of transporters on therapeutic failure, drug resistance, and chemical toxicity
One of the key findings in this study was that ATP Binding Cassette B1 (ABCB1) protein expression does not differ
One of the key findings in this study was that ABCB1 protein expression does not differ significantly in different liver regions; this indicates that random collection of liver tissue is significantly in different liver regions; this indicates that random collection of liver tissue is appropriate appropriate for studying ABCB1 ex vivo
Summary
Interest in active transporters, such as the ATP Binding Cassette (ABC) proteins, has peaked in recent years because they play crucial roles in drug, chemical, hormone, and nutrient disposition [1].Clinical and environmental studies increasingly consider the effects of transporters on therapeutic failure, drug resistance, and chemical toxicity. Interest in active transporters, such as the ATP Binding Cassette (ABC) proteins, has peaked in recent years because they play crucial roles in drug, chemical, hormone, and nutrient disposition [1]. Very few published studies have determined transporter protein dynamics in human liver tissue samples—a critical site of transport action and critical mediator of systemic endo- and xenobiotic levels. This is due to: (i) difficulties in obtaining human liver tissue samples; and (ii) technical challenges working with ABC proteins in the laboratory [2,3,4,5,6,7]. The ABCB1 protein is present on the plasma membrane of almost all tissues of the human body (reviewed [8,9,10,11,12])
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