scholarly journals Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

2017 ◽  
Vol 20 (1) ◽  
pp. 435 ◽  
Author(s):  
Jieyun Cao ◽  
Michael Ng ◽  
Melanie A Felmlee
Keyword(s):  
Sex Differences ◽  
Membrane Protein ◽  
Protein Expression ◽  
Estrous Cycle ◽  
Sex Hormones ◽  
Membrane Trafficking ◽  
Drug Disposition ◽  
Membrane Expression ◽  
Membrane Protein Expression ◽  
Estrous Cycle Stage

Purpose: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females. Method: Liver samples were collected from females at the four estrous cycle stages (proestrus, estrus, metestrus, diestrus), OVX females and male Sprague-Dawley rats (N = 3 – 5). Estrus cycle stage of females was determined by vaginal lavage. mRNA and protein (total and membrane) expression of MCT1, MCT4 and CD147 was evaluated by qPCR and western blot analysis. Results: MCT1 mRNA and membrane protein expression varied with estrous cycle stage, with OVX females having higher expression than males, indicating that female sex hormones may play a role in MCT1 regulation. MCT4 membrane expression varied with estrous cycle stage with expression significantly lower than males. MCT4 membrane expression in OVX females was also lower than males, suggesting that androgens play a role in membrane expression of MCT4. Males had higher membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels suggesting that androgens are involved in regulating CD147 membrane localization. Conclusions: This study demonstrates hepatic expression and membrane localization of MCT1, MCT4 and CD147 are regulated by sex hormones. Sex differences in hepatic MCT expression may lead to altered drug disposition, so it is critical to elucidate the underlying mechanisms in the sex hormone-dependent regulation of MCT expression. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Developmental Expression of Monocarboxylate Transporter 1 and 4 in Rat Liver

2019 ◽  
Vol 22 ◽  
pp. 376-387 ◽  
Author(s):  
Michael Ng ◽  
Justin Louie ◽  
Jieyun Cao ◽  
Melanie A Felmlee
Keyword(s):  
Membrane Protein ◽  
Protein Expression ◽  
Sexual Maturity ◽  
Drug Distribution ◽  
Developmental Expression ◽  
Membrane Expression ◽  
Whole Cell ◽  
Membrane Protein Expression ◽  
Gamma Hydroxybutyrate ◽  
Cd147 Expression

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.

Quantitative Membrane Protein Expression at the Blood–Brain Barrier of Adult and Younger Cynomolgus Monkeys

2011 ◽  
Vol 100 (9) ◽  
pp. 3939-3950 ◽  
Author(s):  
Katsuaki Ito ◽  
Yasuo Uchida ◽  
Sumio Ohtsuki ◽  
Sanshiro Aizawa ◽  
Hirotaka Kawakami ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Protein Expression ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Cynomolgus Monkeys ◽  
Membrane Protein Expression ◽  
Blood Brain

scholarly journals Impact of hydroxycarbamide and interferon-α on red cell adhesion and membrane protein expression in polycythemia vera

Haematologica ◽  
2018 ◽  
Vol 103 (6) ◽  
pp. 972-981 ◽  
Author(s):  
Mégane Brusson ◽  
Maria De Grandis ◽  
Sylvie Cochet ◽  
Sylvain Bigot ◽  
Mickaël Marin ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Membrane Protein ◽  
Protein Expression ◽  
Polycythemia Vera ◽  
Interferon Α ◽  
Red Cell ◽  
Membrane Protein Expression

Database Study on the Expression and Purification of Membrane Proteins

2021 ◽  
Vol 28 ◽  
Author(s):  
Chen-Yan china Zhang ◽  
Shi-Qi Zhao ◽  
Shi-Long Zhang ◽  
Li-Heng Luo ◽  
Ding-Chang Liu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Expression ◽  
Drug Targets ◽  
Expression System ◽  
Data Bank ◽  
Hek293 Cells ◽  
Expression And Purification ◽  
Beta Barrel ◽  
Membrane Protein Expression

: Membrane proteins are crucial for biological processes, and many of them are important to drug targets. Understanding the three-dimensional structures of membrane proteins are essential to evaluate their bio function and drug design. High-purity membrane proteins are important for structural determination. Membrane proteins have low yields and are difficult to purify because they tend to aggregate. We summarized membrane protein expression systems, vectors, tags, and detergents, which have deposited in the Protein Data Bank (PDB) in recent four-and-a-half years. Escherichia coli is the most expression system for membrane proteins, and HEK293 cells are the most commonly cell lines for human membrane protein expression. The most frequently vectors are pFastBac1 for alpha-helical membrane proteins, pET28a for beta-barrel membrane proteins, and pTRC99a for monotopic membrane proteins. The most used tag for membrane proteins is the 6×His-tag. FLAG commonly used for alpha-helical membrane proteins, Strep and GST for beta-barrel and monotopic membrane proteins, respectively. The detergents and their concentrations used for alpha-helical, beta-barrel, and monotopic membrane proteins are different, and DDM is commonly used for membrane protein purification. It can guide the expression and purification of membrane proteins, thus contributing to their structure and bio function studying.

scholarly journals Predicting Membrane Protein Expression in Yeast from Sequence-Derived Features

2017 ◽  
Vol 112 (3) ◽  
pp. 355a-356a
Author(s):  
Samuel J. Schulte ◽  
Shyam Saladi ◽  
William M. Clemons
Keyword(s):  
Membrane Protein ◽  
Protein Expression ◽  
Membrane Protein Expression
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