Journal of Pharmacy & Pharmaceutical Sciences (Jul 2019)
Developmental Expression of Monocarboxylate Transporter 1 and 4 in Rat Liver
Abstract
Purpose: Monocarboxylate transporters (MCT) are proton-coupled integral membrane proteins that control the influx and efflux of endogenous monocarboxylates such as lactate, acetate and pyruvate. They also transport and mediate the clearance of drugs such as valproate and gamma-hydroxybutyrate. CD147 functions as ancillary protein that chaperones MCT1 and MCT4 to the cell membrane. There is limited data on the maturation of MCT and CD147 expression in tissues related to drug distribution and clearance. The objective of the present study was to quantify hepatic MCT1, MCT4, and CD147 mRNA, whole cell and membrane protein expression from birth to sexual maturity. Methods: Liver tissues were collected from male and female Sprague Dawley rats at postnatal days (PND) 1, 3, 5, 7, 10, 14, 18, 21, 28, 35, and 42 (n = 3 - 5). Hepatic mRNA, total and membrane protein expression of MCT1, MCT4, and CD147 was evaluated via qPCR and western blot. Results: MCT1 mRNA and protein demonstrated nonlinear maturation patterns. MCT1 and CD147 membrane protein exhibited low expression at birth, with expression increasing three-fold by PND14, followed by a decline in expression at sexual maturity. MCT4 mRNA had highest expression at PND 1, with decreasing expression towards sexual maturity. In contrast, MCT4 membrane protein exhibited minimal expression from birth through weaning before a 10-fold surge at PND35, whereupon there was a sharp decline in expression at PND42. There was a significant positive correlation between MCT1 and CD147 whole cell and membrane expression, while MCT4 membrane expression demonstrated a weak negative correlation with CD147. Conclusion: Our study elucidates the transcriptional and translational maturation patterns of MCT1, MCT4 and CD147 expression, with isoform-dependent differences in the liver. Changes in transporter expression during development may greatly influence drug distribution and clearance in pediatric populations.
