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.

Effect of Sex and Cross-Sex Hormone Treatment on Renal Monocarboxylate-Transporter Expression in Rats

“…CD147 mediates MCT1 and MCT4 localization, and an absence of CD147 expression results in MCT1 and MCT4 retention in the Golgi apparatus and endoplasmic reticulum [12,33]. A strong significant correlation between the membrane expression of MCT1 and CD147, but a weak correlation between the MCT4 and CD147 from the literature, also supported our observed results [29]. The CST combotreated rats had lower membrane-protein expression levels of MCT1, MCT4 and CD147 compared to the intact females (Figures 2F, 4F and 6F).…”

“…MCT4 mRNA and membrane-protein expression varied significantly in response to female sex and cross-sex hormone treatment. The OVX progesterone rats had lower MCT4 mRNA expression compared to the OVX progesterone placebo group (Figure 3C), suggestive of the progesterone-mediated downregulation of MCT4 mRNA expression in OVX rats, consistent with sex differences observed in the literature [21,29]. Conversely, MCT4 mRNA expression was similar between the CST progesterone and CST progesterone placebo groups (Figure 3D), demonstrating a varied response to female sex hormones following cross-sex hormone treatment.…”

GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats

“…Sample preparation and western blot analysis was previously validated in our laboratory [25,30]. Kidney tissue (20-30 mg) was homogenized in 600 µL ice-cold radioimmunoprecipitation assay buffer (RIPA) containing Protease Inhibitor Cocktail (UltraCruz, Santa Cruz Biotechnology), the ratio between the mass of the tissue (in ug) and the volume of the buffer (in uL) is 33.3:1 to 50:1, to obtain the whole cell protein extract.…”

Decreased Blood Glucose and Lactate: Is a Useful Indicator of Recovery Ability in Athletes?

“…Human, rat and horse muscles express MCTl and MCT4. Both MCT1 and MCT4 need of an ancillary protein CD147 for their activity [52][53][54]. MCT1 and 4 are the predominant MCT transporters in human skeletal muscle while MCT2 is prominently expressed in the liver and brain [55,56].…”