Localization of nucleoside transporters in rat epididymis

Klein, David; Harding, Marcus C.; Crowther, Meghan K; Cherrington, Nathan J.

doi:10.1002/jbt.21911

Cited by 6 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ENT2 was also found to be located in the nuclei of proliferating and differentiated HepaRG cells, suggesting that ENT2 expression at the plasma membrane is probably very weak, which agrees with the low contribution of ENT2 activity to total uridine transport in HepaRG cells. It is noteworthy that nuclear localization of ENT2 has previously been reported in other cell types [43,44] and may be implicated in nuclear uptake of nucleosides [45]. CNT1 protein was detected in differentiated HepaRG cells, but not in proliferating counterparts, which agrees with the mRNA expression profiles of these cells.…”

Section: Discussionsupporting

confidence: 84%

mRNA Expression and Activity of Nucleoside Transporters in Human Hepatoma HepaRG Cells

et al. 2018

View full text Add to dashboard Cite

The HepaRG cell line is a highly differentiated human hepatoma cell line, displaying the expression of various drug transporters. However, functional expression of nucleoside transporters remains poorly characterized in HepaRG cells, although these transporters play a key role in hepatic uptake of antiviral and anticancer drugs. The present study was, therefore, designed to characterize the expression, activity and regulation of equilibrative (ENT) and concentrative (CNT) nucleoside transporter isoforms in differentiated HepaRG cells. These cells were found to exhibit a profile of nucleoside transporter mRNAs similar to that found in human hepatocytes, i.e., notable expression of ENT1, ENT2 and CNT1, with very low or no expression of CNT2 and CNT3. ENT1 activity was, next, demonstrated to be the main uridine transport activity present in HepaRG cells, like in cultured human hepatocytes. Various physiological factors, such as protein kinase C (PKC) activation or treatment by inflammatory cytokines or hepatocyte growth factor (HGF), were additionally found to regulate expression of ENT1, ENT2 and CNT1; PKC activation and HGF notably concomitantly induced mRNA expression and activity of ENT1 in HepaRG cells. Overall, these data suggest that HepaRG cells may be useful for analyzing cellular pharmacokinetics of nucleoside-like drugs in human hepatic cells, especially of those handled by ENT1.

show abstract

Section: Discussionsupporting

confidence: 84%

mRNA Expression and Activity of Nucleoside Transporters in Human Hepatoma HepaRG Cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Transport of drugs across a biological membrane by transporters is often required for drugs to reach their targets efficiently. Transporters have a substantial impact on the disposition and efficacy of xenobiotics and their presence in the MGT (Robillard et al 2012, Fietz et al 2013, Klein et al 2014ab, Klein et al 2015, Klein et al 2017. Simple diffusion, facilitated transport, and secondary active transport move molecules down their electrochemical gradient and do not require energy.…”

Section: Transporters In the Male Genital Tract (Mgt)mentioning

confidence: 99%

Transepithelial transport across the blood–testis barrier

Miller

Cherrington

2018

Reproduction

View full text Add to dashboard Cite

The blood–testis barrier protects developing germ cells by limiting the entry of xenobiotics into the adluminal compartment. There is strong evidence that the male genital tract can serve as a sanctuary site, an area of the body where tumors or viruses are able to survive treatments because most drugs are unable to reach therapeutic concentrations. Recent work has classified the expression and localization of endogenous transporters in the male genital tract as well as the discovery of a transepithelial transport pathway as the molecular mechanism by which nucleoside analogs may be able to circumvent the blood–testis barrier. Designing drug therapies that utilize transepithelial transport pathways may improve drug disposition to this sanctuary site. Strategies that improve disposition into the male genital tract could reduce the rate of testicular relapse, decrease viral load in semen, and improve therapeutic strategies for male fertility.

show abstract

“…For example, in mammals, Cnts have been detected in specialized cells, particularly intestinal and hepatic epithelial cells and testis ( Kato et al, 2005 ; Masino and Boison, 2013 ). Cnts have been identified in rat epididymis and shown to play a role in sperm maturation ( Leung et al, 2001 ; Klein et al, 2017 ). In addition, in a recent study, the deficiency of human Cnt1 has been associated with a newly discovered inborn error of pyrimidine metabolism and organ failure in an infant ( Pérez-Torras et al, 2019 ).…”

Section: Introductionunclassified

Mutation in Drosophila concentrative nucleoside transporter 1 alters spermatid maturation and mating behavior

Maaroufi

Pauchova

Lin

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Concentrative nucleoside transporters (Cnts) are unidirectional carriers that mediate the energy-costly influx of nucleosides driven by the transmembrane sodium gradient. Cnts are transmembrane proteins that share a common structural organization and are found in all phyla. Although there have been studies on Cnts from a biochemical perspective, no deep research has examined their role at the organismal level. Here, we investigated the role of the Drosophila melanogaster cnt1 gene, which is specifically expressed in the testes. We used the CRISPR/Cas9 system to generate a mutation in the cnt1 gene. The cnt1 mutants exhibited defects in the duration of copulation and spermatid maturation, which significantly impaired male fertility. The most striking effect of the cnt1 mutation in spermatid maturation was an abnormal structure of the sperm tail, in which the formation of major and minor mitochondrial derivatives was disrupted. Our results demonstrate the importance of cnt1 in male fertility and suggest that the observed defects in mating behavior and spermatogenesis are due to alterations in nucleoside transport and associated metabolic pathways.

show abstract

Localization of nucleoside transporters in rat epididymis

Cited by 6 publications

References 23 publications

mRNA Expression and Activity of Nucleoside Transporters in Human Hepatoma HepaRG Cells

mRNA Expression and Activity of Nucleoside Transporters in Human Hepatoma HepaRG Cells

Transepithelial transport across the blood–testis barrier

Mutation in Drosophila concentrative nucleoside transporter 1 alters spermatid maturation and mating behavior

Contact Info

Product

Resources

About