scholarly journals Involvement of TauT/SLC6A6 in Taurine Transport at the Blood–Testis Barrier

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Yoshiyuki Kubo ◽  
Sakiko Ishizuka ◽  
Takeru Ito ◽  
Daisuke Yoneyama ◽  
Shin-ichi Akanuma ◽  
...  
Keyword(s):  
Aminobutyric Acid ◽  
Seminiferous Tubules ◽  
Taurine Transporter ◽  
Taurine Transport ◽  
Plot Analysis ◽  
Influx Transport ◽  
Dependent Inhibition ◽  
Taurine Uptake ◽  
Sertoli Cell Line ◽  
Blood Testis Barrier

Taurine transport was investigated at the blood–testis barrier (BTB) formed by Sertoli cells. An integration plot analysis of mice showed the apparent influx permeability clearance of [3H]taurine (27.7 μL/(min·g testis)), which was much higher than that of a non-permeable paracellular marker, suggesting blood-to-testis transport of taurine, which may involve a facilitative taurine transport system at the BTB. A mouse Sertoli cell line, TM4 cells, showed temperature- and concentration-dependent [3H]taurine uptake with a Km of 13.5 μM, suggesting that the influx transport of taurine at the BTB involves a carrier-mediated process. [3H]Taurine uptake by TM4 cells was significantly reduced by the substrates of taurine transporter (TauT/SLC6A6), such as β-alanine, hypotaurine, γ-aminobutyric acid (GABA), and guanidinoacetic acid (GAA), with no significant effect shown by L-alanine, probenecid, and L-leucine. In addition, the concentration-dependent inhibition of [3H]taurine uptake revealed an IC50 of 378 μM for GABA. Protein expression of TauT in the testis, seminiferous tubules, and TM4 cells was confirmed by Western blot analysis and immunohistochemistry by means of anti-TauT antibodies, and knockdown of TauT showed significantly decreased [3H]taurine uptake by TM4 cells. These results suggest the involvement of TauT in the transport of taurine at the BTB.

Identification of a high affinity taurine transporter which is not dependent on chloride

1995 ◽  
Vol 15 (4) ◽  
pp. 231-239 ◽  
Author(s):  
D. B. Shennan
Keyword(s):  
Amino Acids ◽  
Transport System ◽  
Niflumic Acid ◽  
Cell Swelling ◽  
Mammary Tissue ◽  
Taurine Transporter ◽  
Taurine Transport ◽  
High Affinity ◽  
Taurine Uptake

Taurine transport by lactating gerbil mammary tissue has been examined. Taurine uptake is, mediated by a high-affinity system which is specific for β-amino acids. The uptake of taurine is Na+-dependent but appears not to be obligatorly dependent upon Cl−. Thus, replacing Na+ with choline almost abolished taurine uptake. Substituting Cl− with NO3− had no effect whereas SCN− induced a small but significant increase in taurine influx. Taurine uptake was Na+-dependent under conditions where Cl− had been replaced with NO3−. However, it is apparent that the Na+-dependent taurine transport system requires the presence of a permeable anion because replacing Cl− with gluconate markedly reduced taurine uptake. Cell-swelling, induced by a hyposmotic challenge, increased the efflux of taurine from gerbil mammary tissue via a pathway sensitive to niflumic acid.

scholarly journals Human placental taurine transporter in uncomplicated and IUGR pregnancies: cellular localization, protein expression, and regulation

2004 ◽  
Vol 287 (4) ◽  
pp. R886-R893 ◽  
Author(s):  
S. Roos ◽  
T. L. Powell ◽  
T. Jansson
Keyword(s):  
Plasma Membrane ◽  
Protein Expression ◽  
Cellular Localization ◽  
Primary Source ◽  
Fetal Life ◽  
Taurine Transporter ◽  
No Donor ◽  
Taurine Transport ◽  
Placental Protein ◽  
Taurine Uptake

Transplacental transfer is the fetus' primary source of taurine, an essential amino acid during fetal life. In intrauterine growth restriction (IUGR), placental transport capacity of taurine is reduced and fetal taurine levels are decreased. We characterized the protein expression of the taurine transporter (TAUT) in human placenta using immunocytochemistry and Western blotting, tested the hypothesis that placental protein expression of TAUT is reduced in IUGR, and investigated TAUT regulation by measuring the Na+-dependent taurine uptake in primary villous fragments after 1 h of incubation with different effectors. TAUT was primarily localized in the syncytiotrophoblast microvillous plasma membrane (MVM). TAUT was detected as a single 70-kDa band, and MVM TAUT expression was unaltered in IUGR. The PKC activator PMA and the nitric oxide (NO) donor 3-morpholinosydnonimine decreased TAUT activity ( P < 0.05, n = 7–15). However, none of the tested hormones, e.g., leptin and growth hormone, altered TAUT activity significantly. PKC activity measured in MVM from control and IUGR placentas was not different. In conclusion, syncytiotrophoblast TAUT is strongly polarized to the maternal-facing plasma membrane. MVM TAUT expression is unaltered in IUGR, suggesting that the reduced MVM taurine transport in IUGR is due to changes in transporter activity. NO release downregulates placental TAUT activity, and it has previously been shown that IUGR is associated with increased fetoplacental NO levels. NO may therefore play an important role in downregulating MVM TAUT activity in IUGR.

scholarly journals Regulation of taurine transporter activity in LLC-PK1 cells: role of protein synthesis and protein kinase C activation.

1991 ◽  
Vol 2 (5) ◽  
pp. 1021-1029 ◽  
Author(s):  
D P Jones ◽  
L A Miller ◽  
C Dowling ◽  
R W Chesney
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Free Medium ◽  
Taurine Transporter ◽  
Taurine Transport ◽  
Kinase C ◽  
Taurine Uptake ◽  
Protein Kinase C Activation

Taurine transporter activity increases after exposure of cultured renal epithelial cells to taurine-free medium for 24 h and decreases after incubation in high (500 microM) taurine. This adaptive response mimics that observed in rat kidney after manipulation of dietary taurine. In order to elucidate potential mechanisms involved in the regulation of beta-amino acid transporter activity, the role of RNA transcription, protein synthesis, and protein import (trafficking), as well as protein kinase C activation, on the control of taurine transport was examined in the continuous proximally derived LLC-PK1 renal cell line. Inhibition of RNA transcription with actinomycin D did not alter the up-regulatory and down-regulatory adaptive responses. Inhibition of protein synthesis with cycloheximide prevented the increased taurine transport in response to taurine-free medium as well as the decrease in taurine transport after exposure to high taurine. Colchicine prevented the response to taurine-free medium but had no effect on the response to high-taurine medium. Exposure of confluent cell monolayers to the active phorbol esters, phorbol 12-myristate 13-acetate and phorbol 12,13 dibutyrate, resulted in a reduction in taurine uptake. The effect was seen within minutes of exposure but was not observed in the presence of the inactive phorbol 4-alpha. This inhibitory action was blocked by staurosporin, an inhibitor of protein kinase C (PKC). Treatment of cells with the diacylglycerol kinase inhibitor R59022, which results in increased intracellular diacylglycerol, a natural stimulant of PKC, also inhibited taurine uptake, providing further evidence for a specific effect of PKC activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Heat Stress and Pulsed Unfocused Ultrasound: The Viability of these Physical Approaches for Drug Delivery into Testicular Seminiferous Tubules

2020 ◽  
Vol 17 (5) ◽  
pp. 438-446 ◽  
Author(s):  
Yuanyuan Li ◽  
Mohammad Ishraq Zafar ◽  
Xiaotong Wang ◽  
Xiaofang Ding ◽  
Honggang Li
Keyword(s):  
Drug Delivery ◽  
Heat Stress ◽  
Targeted Drug Delivery ◽  
Therapeutic Agents ◽  
Seminiferous Tubules ◽  
Adult Mice ◽  
Targeted Drug ◽  
To Receive ◽  
Unfocused Ultrasound ◽  
Blood Testis Barrier

Aim: To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice. Background: The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects. Objectives: To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules. Material & Methods: Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules. Results: As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS. Conclusion: The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.

Food-grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood-testis barrier disruption in mice

2019 ◽  
Vol 39 (11) ◽  
pp. 1586-1605 ◽  
Author(s):  
Juan Carlos Rodríguez-Escamilla ◽  
Estefany I. Medina-Reyes ◽  
Carolina Rodríguez-Ibarra ◽  
Alejandro Déciga-Alcaraz ◽  
José O. Flores-Flores ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Germ Cells ◽  
Seminiferous Tubules ◽  
Liquid Matrix ◽  
Food Grade ◽  
Barrier Disruption ◽  
Blood Testis Barrier

Characteristics of renal transport of taurine in reptilian brush-border membranes

1991 ◽  
Vol 260 (5) ◽  
pp. R879-R888 ◽  
Author(s):  
S. Benyajati ◽  
J. L. Johnson
Keyword(s):  
Brush Border ◽  
Thamnophis Sirtalis ◽  
Equilibrium Conditions ◽  
Taurine Transport ◽  
Brush Border Membranes ◽  
Renal Brush Border Membranes ◽  
Negative Membrane Potential ◽  
Taurine Uptake ◽  
Filtration Technique

We examined characteristics of taurine transport across renal brush-border membranes (BBM) of the garter snake (Thamnophis sirtalis), a species that demonstrates both net reabsorption and secretion of taurine in vivo. Transport was examined by a rapid filtration technique at 25 degrees C. Inwardly directed Na+ gradient specifically stimulated taurine uptake. Under initial taurine equilibrium condition, a small overshoot of taurine uptake driven by an inwardly directed NaCl gradient could be observed. No stimulation of taurine uptake was observed under Na+ equilibrium or K+, Li+, or choline gradients conditions. Reptilian renal BBM taurine transport also displayed specific Cl- requirement: replacement of NaCl by NaSCN or Na(+)-gluconate gradients inhibited taurine uptake. The uptake was stimulated under Cl- gradient compared with Cl- equilibrium conditions. Taurine transport was not stimulated by H+ gradient in either direction, although it was inhibited by acidic pH (less than 7.0). Amiloride and furosemide had no effects. The transport was electrogenic, stimulated by an inside negative membrane potential, and inhibited by other beta-amino acids. Overall, the reptilian BBM transport system for taurine resembles those observed in both mammalian and fish renal BBM.

scholarly journals Generation of a hTERT-Immortalized Human Sertoli Cell Model to Study Transporter Dynamics at the Blood-Testis Barrier

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1005
Author(s):  
Raymond K. Hau ◽  
Siennah R. Miller ◽  
Stephen H. Wright ◽  
Nathan J. Cherrington
Keyword(s):  
Mrna Expression ◽  
Cell Model ◽  
In Vitro Models ◽  
Replication Capacity ◽  
Seminiferous Tubules ◽  
Difference Threshold ◽  
Transport Pathways ◽  
Equilibrative Nucleoside Transporters ◽  
Blood Testis Barrier

The blood-testis barrier (BTB) formed by adjacent Sertoli cells (SCs) limits the entry of many chemicals into seminiferous tubules. Differences in rodent and human substrate-transporter selectivity or kinetics can misrepresent conclusions drawn using rodent in vitro models. Therefore, human in vitro models are preferable when studying transporter dynamics at the BTB. This study describes a hTERT-immortalized human SC line (hT-SerC) with significantly increased replication capacity and minor phenotypic alterations compared to primary human SCs. Notably, hT-SerCs retained similar morphology and minimal changes to mRNA expression of several common SC genes, including AR and FSHR. The mRNA expression of most xenobiotic transporters was within the 2-fold difference threshold in RT-qPCR analysis with some exceptions (OAT3, OCT3, OCTN1, OATP3A1, OATP4A1, ENT1, and ENT2). Functional analysis of the equilibrative nucleoside transporters (ENTs) revealed that primary human SCs and hT-SerCs predominantly express ENT1 with minimal ENT2 expression at the plasma membrane. ENT1-mediated uptake of [3H] uridine was linear over 10 min and inhibited by NBMPR with an IC50 value of 1.35 ± 0.37 nM. These results demonstrate that hT-SerCs can functionally model elements of transport across the human BTB, potentially leading to identification of other transport pathways for xenobiotics, and will guide drug discovery efforts in developing effective BTB-permeable compounds.

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