scholarly journals Epithelial sodium channel (ENaC) in GtoPdb v.2021.2

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Israel Hanukoglu
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Respiratory Tract ◽  
Reproductive Tract ◽  
Basolateral Membrane ◽  
Water Channel ◽  
Extracellular Fluid ◽  
Female Reproductive Tract ◽  
Filament Bundles ◽  
Na Ions

The epithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the kidney tubules, lung, respiratory tract, male and female reproductive tracts, sweat and salivary glands, placenta, colon, and some other organs [9, 13, 22, 21, 42]. In these epithelia, Na+ ions flow from the extracellular fluid into the cytoplasm of epithelial cells via ENaC. The Na+ ions are then pumped out of the cytoplasm into the interstitial fluid by the Na+/K+ ATPase located on the basolateral membrane [36]. As Na+ is one of the major electrolytes in the extracellular fluid (ECF), osmolarity change initiated by the Na+ flow is accompanied by a flow of water accompanying Na+ ions [6]. Thus, ENaC has a central role in regulating ECF volume and blood pressure, primarily via its function in the kidney [37]. The expression of ENaC subunits, hence its activity, is regulated by the renin-angiotensin-aldosterone system, and other factors involved in electrolyte homeostasis [37, 30]. In the respiratory tract and female reproductive tract, large segments of the epithelia are composed of multi-ciliated cells. In these cells, ENaC is located along the entire length of the cilia that cover the cell surface [15]. Cilial location greatly increases ENaC density per cell surface and allows ENaC to serve as a sensitive regulator of osmolarity of the periciliary fluid throughout the whole depth of the fluid bathing the cilia [15]. In contrast to ENaC, CFTR (ion transporter defective in cystic fibrosis) is located on non-cilial cell-surface [15]. In the vas deferens segment of the male reproductive tract, the luminal surface is covered by microvilli and stereocilia projections with backbones composed of actin filament bundles [42]. In these cells, both ENaC and the water channel aquaporin AQP9 are localized on these projections and also in the basal and smooth muscle layers [42]. Thus, ENaC function is also essential for the clearance of respiratory airways, transport of germ cells, fertilization, implantation, and cell migration [15, 22].

scholarly journals Epithelial sodium channel (ENaC) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Israel Hanukoglu
Keyword(s):  
Cell Surface ◽  
Respiratory Tract ◽  
Reproductive Tract ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Female Reproductive Tract ◽  
Epithelial Sodium Channels ◽  
Rare Mutations ◽  
Na Ions ◽  
Epithelial Sodium Channel Enac

The epithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the distal kidney tubules, lung, respiratory tract, male and female reproductive tracts, sweat and salivary glands, placenta, colon and some other organs [20, 11, 7]. In these epithelia, ENaC allows flow of Na+ ions from the extracellular fluid in the lumen into the epithelial cell. Na+ ions are then pumped out of the cytoplasm into the interstitial fluid by the Na+/K+ ATPase located on the basolateral membrane [39]. As Na+ is one of the major electrolytes in the extracellular fluid (ECF), osmolarity change initiated by the Na+ flow is accompanied by a flow of water accompanying Na+ ions [6]. Thus, ENaC has a central role in the regulation of ECF volume and blood pressure, especially via its function in the kidney [25, 30]. The expression of ENaC subunits, hence its activity, is regulated by the renin-angotensin-aldosterone system, and other factors that are involved in electrolyte homeostasis [30, 1, 29]. In the respiratory tract and female reproductive tract large segments of the tracts are covered by multi-ciliated cells. In these cells ENaC has been shown to be located along the entire length of the cilia [14]. Cilial location greatly increases ENaC density per cell surface and allows ENaC to serve as a sensitive regulator of osmolarity of the periciliary fluid throughout the whole depth of the fluid bathing the cilia [14]. In contrast to ENaC, CFTR that is defective in cystic fibrosis is not located on non-cilial cell-surface [14]. Thus, ENaC function is also essential for the clearance of respiratory airways, transport of germ cells, fertilization, implantation and cell migration [14, 33]. ENaC has been recently localized in the germinal epithelium of the testis, Sertoli cells, spermatozoa, along the epididymis ducts, and smooth muscle cells [35, 36]. Evidence has been provided that rare mutations in ENaC are associated with female infertility [5].

Epithelial sorting of a glycosylphosphatidylinositol-anchored bacterial protein expressed in polarized renal MDCK and intestinal Caco-2 cells

1995 ◽  
Vol 108 (1) ◽  
pp. 369-377 ◽  
Author(s):  
K.L. Soole ◽  
M.A. Jepson ◽  
G.P. Hazlewood ◽  
H.J. Gilbert ◽  
B.H. Hirst
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Intestinal Epithelial Cells ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Apical Cell ◽  
Apical Surface ◽  
Intestinal Epithelial ◽  
Gpi Anchor ◽  
Sorting Signal

To evaluate whether a glycosylphosphatidylinositol (GPI) anchor can function as a protein sorting signal in polarized intestinal epithelial cells, the GPI-attachment sequence from Thy-1 was fused to bacterial endoglucanase E' (EGE') from Clostridium thermocellum and polarity of secretion of the chimeric EGE'-GPI protein was evaluated. The chimeric EGE'-GPI protein was shown to be associated with a GPI anchor by TX-114 phase-partitioning and susceptibility to phosphoinositol-specific phospholipase C. In polarized MDCK cells, EGE' was localized almost exclusively to the apical cell surface, while in polarized intestinal Caco-2 cells, although 80% of the extracellular form of the enzyme was routed through the apical membrane over a 24 hour period, EGE' was also detected at the basolateral membrane. Rates of delivery of EGE'-GPI to the two membrane domains in Caco-2 cells, as determined with a biotinylation protocol, revealed apical delivery was approximately 2.5 times that of basolateral. EGE' delivered to the basolateral cell surface was transcytosed to the apical surface. These data indicate that a GPI anchor does represent a dominant apical sorting signal in intestinal epithelial cells. However, the mis-sorting of a proportion of EGE'GPI to the basolateral surface of Caco-2 cells provides an explanation for additional sorting signals in the ectodomain of some endogenous GPI-anchored proteins.

scholarly journals Effects of Tenofovir on Cytokines and Nucleotidases in HIV-1 Target Cells and the Mucosal Tissue Environment in the Female Reproductive Tract

2014 ◽  
Vol 58 (11) ◽  
pp. 6444-6453 ◽  
Author(s):  
Nabanita Biswas ◽  
Marta Rodriguez-Garcia ◽  
Zheng Shen ◽  
Sarah G. Crist ◽  
Jack E. Bodwell ◽  
...  
Keyword(s):  
T Cells ◽  
Biological Activity ◽  
Epithelial Cells ◽  
Hiv Infection ◽  
Proinflammatory Cytokines ◽  
Reproductive Tract ◽  
Biological Activities ◽  
Female Reproductive Tract ◽  
Immune Protection ◽  
Tnf Α

ABSTRACTTenofovir (TFV) is a reverse transcriptase inhibitor used in microbicide preexposure prophylaxis trials to prevent HIV infection. Recognizing that changes in cytokine/chemokine secretion and nucleotidase biological activity can influence female reproductive tract (FRT) immune protection against HIV infection, we tested the hypothesis that TFV regulates immune protection in the FRT. Epithelial cells, fibroblasts, CD4+T cells, and CD14+cells were isolated from the endometrium (Em), endocervix (Cx), and ectocervix (Ecx) following hysterectomy. The levels of proinflammatory cytokines (macrophage inflammatory protein 3α [MIP-3α], interleukin 8 [IL-8], and tumor necrosis factor alpha [TNF-α]), the expression levels of specific nucleotidases, and nucleotidase biological activities were analyzed in the presence or absence of TFV. TFV influenced mRNA and/or protein cytokines and nucleotidases in a cell- and site-specific manner. TFV significantly enhanced IL-8 and TNF-α secretion by epithelial cells from the Em and Ecx but not from the Cx. In contrast, in response to TFV, IL-8 secretion was significantly decreased in Em and Cx fibroblasts but increased with fibroblasts from the Ecx. When incubated with CD4+T cells from the FRT, TFV increased IL-8 (Em and Ecx) and TNF-α (Cx and Ecx) secretion levels. Moreover, when incubated with Em CD14+cells, TFV significantly increased MIP-3α, IL-8, and TNF-α secretion levels relative to those of the controls. In contrast, nucleotidase biological activities were significantly decreased by TFV in epithelial (Cx) and CD4+T cells (Em) but increased in fibroblasts (Em). Our findings indicate that TFV modulates proinflammatory cytokines, nucleotidase gene expression, and nucleotidase biological activity in epithelial cells, fibroblasts, CD4+T cells, and CD14+cells at distinct sites within the FRT.

scholarly journals Estradiol Regulation of Nucleotidases in Female Reproductive Tract Epithelial Cells and Fibroblasts

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69854 ◽  
Author(s):  
Zheng Shen ◽  
John V. Fahey ◽  
Jack E. Bodwell ◽  
Marta Rodriguez-Garcia ◽  
Richard M. Rossoll ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Reproductive Tract ◽  
Female Reproductive Tract

scholarly journals Trichomonas vaginalis Lipophosphoglycan Triggers a Selective Upregulation of Cytokines by Human Female Reproductive Tract Epithelial Cells

2006 ◽  
Vol 74 (10) ◽  
pp. 5773-5779 ◽  
Author(s):  
Raina N. Fichorova ◽  
Radiana T. Trifonova ◽  
Robert O. Gilbert ◽  
Catherine E. Costello ◽  
Gary R. Hayes ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Trichomonas Vaginalis ◽  
Reproductive Tract ◽  
Adaptor Protein ◽  
Dendritic Cell Maturation ◽  
Female Reproductive Tract ◽  
Dependent Manner ◽  
Sexually Transmitted ◽  
Vaginal Epithelial Cells ◽  
Dose Dependent

ABSTRACT Trichomonas vaginalis is one of the most common nonviral sexually transmitted human infections and, worldwide, has been linked to increased incidence of human immunodeficiency virus type 1 transmission, preterm delivery, low birth weight, cervical cancer, and vaginitis. The molecular pathways that are important in initiating host inflammatory and immune responses to T. vaginalis are poorly understood. Here we report interactions of human cervicovaginal epithelial cells with the most abundant cell surface glycoconjugate of the parasite, the T. vaginalis lipophosphoglycan (LPG). Purified LPG mediated the adhesion of parasites to human vaginal epithelial cells in a dose-dependent manner. Furthermore, T. vaginalis LPG (but not LPG from Tritrichomonas foetus, the causative agent of bovine trichomoniasis) induced a selective upregulation of chemotactic cytokines by human endocervical, ectocervical, and vaginal epithelial cells, which do not express Toll-like receptor 4/MD2. The T. vaginalis LPG triggered interleukin 8 (IL-8), which promotes the adhesion and transmigration of neutrophils across the endothelium, and macrophage inflammatory protein 3α, which is a chemoattractant for immune cells and is essential for dendritic cell maturation. These effects were dose dependent and sustained in the absence of cytotoxicity and IL-1β release and utilized, at least in part, a signaling pathway independent from the Toll-like/IL-1 receptor adaptor protein MyD88.

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