Abanda Ngu Njei, Riches Zoe, Collier Abby C
Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii, Honolulu, HI 96813, USA.
Biotechnology Center, University of Yaoundé I, Yaoundé, Cameroon.
Pharmaceutics. 2017 Feb 17;9(1):8. doi: 10.3390/pharmaceutics9010008.
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 ( = 24, 18-69 years), and in S9 from randomly acquired samples ( = 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 ( < 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.
ATP结合盒转运体B1（ABCB1）在体内外源性物质的效能和毒性方面发挥着关键作用。为了解肝脏转运中的人群变异性，我们测定了从8个预定义位点采集的全肝裂解物（n = 24，年龄18 - 69岁）以及随机采集样本的S9组分（n = 87，年龄7天 - 87岁）中的ABCB1 mRNA和蛋白水平。ABCB1水平在个体肝脏中无显著差异，个体间蛋白水平差异达4.4倍。裂解物或S9组分中的mRNA和蛋白水平均不随性别、种族、肥胖或甘油三酯水平而变化（二者呈现相同关系），但儿科S9组分中的蛋白水平较低（P < 0.0001），出生时ABCB1水平为成人的76%，预计5年后成熟。未获取到儿科全肝裂解物。总之，通过机会性采集来研究人类肝脏ABCB1是可行的。此外，儿童的ABCB1水平可能较低，这表明该特殊人群在毒性和治疗反应方面具有不同的潜力。
