Nucleoside Transport at the Blood-Testis Barrier Studied with Primary-Cultured Sertoli Cells

Kato, Ryo; Maeda, Tomoji; Akaike, Toshihiro; Tamai, Ikumi

doi:10.1124/jpet.104.073387

Cited by 45 publications

(59 citation statements)

References 43 publications

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“…Although Sertoli cells extend from the basal compartment into the adluminal compartment, the two tubular compartments are separated by junctional complexes (tight and adherens junctions) between neighbouring Sertoli cells, that function as the major component of the blood-testis barrier Dym & Fawcett, 1971;Russell, 1977;Holash et al, 1993;Li et al, 2006). This barrier, dividing the seminiferous epithelium, selectively restricts the passage of many substances contained in the general circulation (Dym, 1973, Pelletier & Byers, 1992Kato et al, 2005;Li et al, 2006). The integrity of the bloodtestis barrier is a prerequisite for normal spermatogenesis.…”

Section: Compartmentalization and The Blood-testis Barriermentioning

confidence: 99%

Vitamin C and oxidative stress in the seminiferous epithelium

et al. 2011

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In this article, we focus on the fundamental role of vitamin C transporters for the normal delivery of vitamin C to germ cells in the adluminal compartment of seminiferous tubules. We argue that the redox status within spermatozoa or in semen is partly responsible for the etiology of infertility. In this context, antioxidant defence plays a critical role in male fertility. Vitamin C, a micronutrient required for a wide variety of metabolic functions, has long been associated with male reproduction. Two systems for vitamin C transport have been described in mammals. Facilitative hexose transporters (GLUTs), with 14 known isoforms to date, GLUT1-GLUT14, transport the oxidized form of vitamin C (dehydroascorbic acid) into the cells. Sodium ascorbic acid co-transporters (SVCTs), SVCT1 and SVCT2 transport the reduced form of vitamin C (ascorbic acid). Sertoli cells control germ cell proliferation and differentiation through cell-cell communication and form the blood-testis barrier. Because the blood-testis barrier limits direct access of molecules from the plasma into the adluminal compartment of the seminiferous tubule, one important question is the method by which germ cells obtain vitamin C. Some interesting results have thrown light on this matter. Expression of SVCT2 and some isoforms of GLUT transporters in the testis have previously been described. Our group has demonstrated that Sertoli cells express functionally active vitamin C transporters. Kinetic characteristics were described for both transport systems (SVCT and GLUT systems). Sertoli cells are able to transport both forms of vitamin C. These fi ndings are extremely relevant, because Sertoli cells may control the amount of vitamin C in the adluminal compartment, as well as regulating the availability of this metabolite throughout spermatogenesis.

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Section: Compartmentalization and The Blood-testis Barriermentioning

confidence: 99%

Vitamin C and oxidative stress in the seminiferous epithelium

et al. 2011

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“…Uptake of carnitine in suspended primary-cultured rat epididymal epithelial cells was examined using the same method as in a previous study with primary-cultured Sertoli cells (Kato et al 2005, Kobayashi et al 2005. Briefly, primary-cultured epididymal epithelial cells were harvested with a cell scraper and suspended in transport medium containing 137 mM NaCl, 5 mM KCl, 0.39 mM NaHCO 3 , 0.44 mM KH 2 PO 4 , 0.95 mM CaCl 2 , 0.8 mM MgSO 4 , 25 mM D-glucose and 10 mM HEPES, adjusted to pH 7.4.…”

Section: Carnitine Transport Experimentsmentioning

confidence: 99%

Carnitine/organic cation transporter OCTN2-mediated transport of carnitine in primary-cultured epididymal epithelial cells

Kobayashi¹,

Irokawa²,

Maeda³

et al. 2005

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Carnitine is essential for the acquisition of motility and maturation of spermatozoa in the epididymis, and is accumulated in epididymal fluid. In this study, carnitine transport into primary-cultured rat epididymal epithelial cells was characterized to clarify the nature of the transporter molecules involved. Uptake of carnitine by primary-cultured epididymal epithelial cells was time, Na 1 and concentration dependent. Kinetic analysis of carnitine uptake by the cells revealed the involvement of high-and low-affinity transport systems with Km values of 21 mM and 2.2 mM respectively. The uptake of carnitine by the cells was significantly reduced by inhibitors of carnitine/organic cation transporter (OCTN2), such as carnitine analogues and cationic compounds. In RT-PCR analysis, OCTN2 expression was detected. These results demonstrated that the high-affinity carnitine transporter OCTN2, which is localized at the basolateral membrane of epididymal epithelial cells, mediates carnitine supply into those cells from the systemic circulation as the first step of permeation from blood to spermatozoa.Reproduction (

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“…MRP8 is known to play a role in ear wax synthesis, auxiliary body odor, and breast cancer due to the transport of many pro-growth hormones and amino acids (Guo et al, 2003;Bortfeld et al, 2006;Kruh et al, 2007). In the testis, it has been speculated that these transporters contribute to keeping xenobiotic compounds out of the BTB, thereby protecting dividing germ cells from potential toxicants (Kato et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis

2013

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The blood-testis barrier (BTB) prevents the entry of many drugs into seminiferous tubules, which can be beneficial for therapy not intended for the testis but may decrease drug efficacy for medications requiring entry to the testis. Previous data have shown that some of the transporters in the multidrug resistance-associated protein (MRP) family (ABCC) are expressed in the testis. By determining the subcellular localization of these transporters, their physiologic function and effect on drug disposition may be better predicted. Using immunohistochemistry (IHC), we determined the site of expression of the MRP transporters expressed in the testis, namely, MRP1, MRP4, MRP5, and MRP8, from immature and mature rats, rhesus macaques, and adult humans. We determined that in all species MRP1 was restricted to the basolateral membrane of Sertoli cells, MRP5 is located in Leydig cells, and MRP8 is located in round spermatids, whereas MRP4 showed speciesspecific localization. MRP4 is expressed on the basolateral membrane of Sertoli cells in human and nonhuman primates, but on the apical membrane of Sertoli cells in immature and mature rats, representing a potential caution when using rat models as a means for studying drug disposition across the BTB. These data suggest that MRP1 may limit drug disposition into seminiferous tubules, as may MRP4 in human and nonhuman primates but not in rats. These data also suggest that MRP5 and MRP8 may not have a major impact on the penetration of drugs across the BTB.

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Nucleoside Transport at the Blood-Testis Barrier Studied with Primary-Cultured Sertoli Cells

Cited by 45 publications

References 43 publications

Vitamin C and oxidative stress in the seminiferous epithelium

Vitamin C and oxidative stress in the seminiferous epithelium

Carnitine/organic cation transporter OCTN2-mediated transport of carnitine in primary-cultured epididymal epithelial cells

Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis

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