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Epithelial sodium channel (ENaC) in GtoPdb v.2025.4
Full text linkOverviewEpithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the kidney tubules, lungs, respiratory tract, male and female reproductive tracts, sweat and salivary glands, placenta, colon, and several other organs [10, 17, 26, 25, 57]. In these epithelia, Na+ ions enter epithelial cells from the extracellular fluid via ENaC and are subsequently pumped out into the interstitial fluid by the Na+/K+-ATPase on the basolateral membrane [49]. Because sodium is a major electrolyte in the extracellular fluid (ECF), the osmotic changes caused by sodium flux are accompanied by parallel water movement [7]. Thus, ENaC plays a central role in regulating ECF volume and blood pressure, primarily through its function in the kidney [51]. The expression of ENaC subunits- and therefore its activity- is controlled by the renin-angiotensin-aldosterone system and other factors involved in electrolyte homeostasis [51, 36]. Genetic studies of systemic pseudohypoaldosteronism type I revealed that ENaC activity depends on three essential subunits encoded by three separate genes encoding homologous proteins [12, 26]. Within the wider protein superfamily that includes ENaC, the first crystal structure determined was that of ASIC, which revealed a trimeric structure with a large extracellular domain anchored in the membrane by a bundle of six transmembrane helices (two per subunit) [3, 30]. The first 3D structure of human ENaC was determined using single-particle cryo-electron microscopy at 3.7Å resolution [45], later improved to 3.0Å [46]. These structures confirmed that ENaC has a quaternary structure similar to ASIC. ENaC assembles as a heterotrimer, with α-, γ-, and β-subunits arranged in clockwise order when viewed from above [13]. In contrast to ASIC1, which can form a functional homotrimer, ENaC is only fully functional as a heterotrimer composed of either αβγ or δβγ [33]. Recently, Houser and Baconguis co-expressed human δ, β, and γ and determined the structures of complexes using single-particle cryoelectron microscopy. The structures showed that β and γ positions are conserved among the different complexes while the α position in the αβγ trimer is occupied by either δ or another β [29]. In the respiratory and female reproductive tracts, large regions of the epithelium consist of multiciliated cells with a microtubule-based cytoskeleton. In these cells, ENaC is distributed along the entire length of the cilia [19]. This localization substantially increases ENaC density on the cell surface and enables precise regulation of periciliary fluid osmolarity throughout its depth [19]. In the vas deferens of the male reproductive tract, the luminal surface is covered with microvilli and stereocilia supported by actin bundles [57]. In these cells, both ENaC and the aquaporin AQP9 are localized to the projections as well as to the basal and smooth muscle layers [57]. In contrast, CFTR- the chloride channel defective in cystic fibrosis- is confined to the apical cell surface but is absent from cilia and microvilli [19, 57]. Collectively, ENaC function regulates epithelial fluid volume, which is essential for mucociliary clearance in the respiratory tract, gamete transport, fertilization, implantation, and cell migration [19, 44, 26]. Genes and PhylogenyThe human genome contains four homologous genes (SCNN1A, SCNN1B, SCNN1G, and SCNN1D) encoding the α-, β-, γ-, and δ-ENaC subunits, respectively [11, 40, 55, 62]. These subunits share 23–34% sequence identity and <20% identity with ASIC subunits [26]. Genes encoding all four ENaC subunits are present in bony vertebrates, except in ray-finned fishes, which have lost them entirely. The mouse genome has also lost SCNN1D, the gene for δ-ENaC [21, 26]. The α-, β-, and γ-ENaC genes are present in jawless vertebrates (e.g., lampreys) and cartilaginous fishes (e.g., sharks) [26]. Methylation analysis of the 5′-flanking regions of SCNN1A, SCNN1B, and SCNN1G in human cells revealed an inverse correlation between gene expression and DNA methylation, suggesting epigenetic transcriptional control of ENaC genes [48]. Channel biogenesis, assembly and functionENaC subunit expression is regulated primarily by aldosterone and by numerous other extracellular and intracellular factors [51, 35, 47]. Most studies indicate that expression of the three subunits is not tightly coordinated [9]. However, transport of the subunits to the membrane requires all three intact subunits, and even a single missense mutation can reduce the number of assembled channels on the cell surface [18]. ENaC is constitutively active, meaning Na+ flow does not require an activating factor. Thus, heterologous cells expressing ENaC (e.g., human cRNAs in Xenopus oocytes) must be maintained in amiloride-containing solutions to block channel activity. ENaC activity is then measured by replacing the bath with amiloride-free solution. The channel alternates between two states: 1) open and 2) closed. The probability of ENaC being open is referred to as open probability (Po). ENaC regulation involves two key parameters: (1) membrane channel density and (2) open probability [31, 33]. Open probability is markedly reduced by extracellular Na+ in a process known as sodium self-inhibition [4, 28, 59]. A key regulatory feature is that the α- and γ-subunits contain conserved extracellular serine protease cleavage sites [26]. Proteolytic cleavage by enzymes such as furin and plasmin activates ENaC [52, 34, 1]. Diseases associated with ENaC mutationsMutations in SCNN1A, SCNN1B, or SCNN1G can cause partial or complete loss of ENaC activity [12, 23]. Such loss-of-function mutations are associated with systemic or multi-system autosomal recessive pseudohypoaldosteronism type I (OMIM abbreviation: PHA1B) [22, 12, 26, 64, 19, 54]. No PHA-causing mutations have been identified in SCNN1D. Patients with PHA experience severe salt wasting in all aldosterone target organs expressing ENaC, including kidney, sweat glands, salivary glands, and respiratory tract. In infancy and early childhood, the resulting electrolyte disturbances, dehydration, and acidosis often require recurrent hospitalization. The frequency and severity of salt-wasting episodes generally improve with age [24]. PHA1B also affects female reproductive system function [19, 6]. The ENaC carboxy-terminal region contains a short consensus sequence called the PY motif. Mutations in this motif in SCNN1B and SCNN1G are associated with Liddle syndrome, a disorder marked by early-onset hypertension [60, 5]. The PY motif is recognized by Nedd4-2, a ubiquitin ligase. Mutations that disrupt this recognition reduce ENaC ubiquitylation, leading to channel accumulation at the membrane and increased ENaC activity [53]. ENaC expression in tumorsIntracellular sodium concentrations are often elevated in cancer cells compared with normal cells, leading to the hypothesis that ENaC overexpression may contribute to metastasis [39]. However, RNA-seq analysis of ENaC genes and clinical data of cervical cancer patients from The Cancer Genome Atlas (TCGA) revealed a negative correlation with histologic grades of tumor [61]. Similarly, in breast cancer cells, overexpression or siRNA-mediated knockdown of α-ENaC showed that higher α-ENaC levels suppress cell proliferation [63]. In contrast, TCGA data showed that elevated SCNN1A expression correlates with poor prognosis in ovarian cancer [41]. Thus, the role of ENaC in tumorigenesis appears to be tissue-specific. COVID-19SARS-CoV-2 virions, the cause of COVID-19, are covered with glycosylated spike (S) proteins. These proteins bind to membrane-bound ACE2 as the first step of viral entry. Entry depends on S-protein cleavage (at Arg-667/Ser-668) by a serine protease. Anand et al. identified a sequence motif at this cleavage site homologous to the furin cleavage site in ENaCα [2]. A comprehensive review of COVID-19 pathophysiology suggests a role for ENaC in the early stages of infection in respiratory epithelia [20]. ENaC Inhibitors for Cystic Fibrosis Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disorder among Caucasians. CF is caused by mutations in the gene that codes for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). CFTR is a chloride and bicarbonate channel located on the apical membrane [14]. CFTR-mediated movement of Cl- and HCO3- ions into the lumen also drives water flow into the lumen by osmosis. CFTR is expressed in many tissues but the most severe effect of mutated CFTR is observed in the respiratory tract in the form of airway surface liquid (ASL) depletion which leads to mucus accumulation, inflammation and bacterial infections that lead to mortality. Normal CFTR activity inhibits ENaC by causing a reduction in surface expression of ENaC as well as its Po [50]. In many epithelia, ENaC and CFTR are not co-localized on the apical membrane indicating that the two channels do not directly interact [19, 56, 57]. In the absence of a functional CFTR, ENaC activity increases (also named as "hyperactivated ENaC"), leading to increased Na+ and water absorption and consequently ASL depletion. These observations have led to the development of inhibitors targeting ENaC in the airways to ameliorate ASL dehydration [58, 43, 38]. Most of the ENaC inhibitors in development are designed for application by inhalation and improved lung retention to avoid damaging the vital activity of ENaC in other tissues [37, 16]. Despite the development of many ENaC inhibitors for CF [15], nearly all drug candidates were discontinued at Preclinical, Phase 1 or Phase 2 stage of clinical trials [38, 16, 43]. However, there is one candidate, EDT001, that is still under Phase 2 clinical trial [16]. The persistence of the scientists and the drug companies and the versatility of their approaches provide hope that an appropriate useful treatment will emerge to help CF patients. Thus, insights into the physiological and pathological roles of ENaC across diverse tissues continue to guide the development of targeted inhibitors, with cystic fibrosis representing a prominent example where modulation of ENaC activity may translate fundamental biology into therapeutic benefit
Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells.
Full text linkWe studied the kinetics of ACTH induction of mitochondrial P450scc, P450c11 and their electron transport proteins, adrenodoxin, and adrenodoxin reductase in bovine adrenal cortex cells in primary culture. The mRNA levels of these enzymes increase and reach a peak within 3-12 h after ACTH addition. The protein levels of adrenodoxin reductase and P450scc show an increase only nearly 24 h after ACTH addition. After ACTH addition, the intracellular level of cAMP reaches maximal levels within 5 min, and then decreases gradually over 60 min. Hence, we examined the effect of a pulse of ACTH or cAMP analogs on enzyme and mRNA levels. Exposure of the cells to ACTH for 1-2 h was sufficient for maximal induction of the enzymes and P450scc mRNA. In contrast, the induction of the enzymes and the mRNA by cAMP analogs or forskolin required the continuous presence of these agents for over 12 h. But, these agents stimulated cortisol secretion to the medium quickly, indicating that they can activate some intracellular processes while not showing any effect on enzyme induction. The absence of any effect of prolonged cAMP pulses on enzyme and mRNA levels weakens the previous hypothesis that cAMP is the sole second messenger for the ACTH induction of steroidogenic enzymes in adrenal cortex cells. The inductive ability of a brief pulse of ACTH indicates that ACTH can rapidly initiate a series of reactions that result in enzyme induction many hours later
Epithelial sodium channel (ENaC) in GtoPdb v.2021.2
Full text linkThe 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]
Steroidogenic Enzymes: Structure, function, and role in regulation of steroid hormone biosynthesis
No full textIn the pathways of steroid hormone biosynthesis there are two major types of enzymes: cytochromes P450 and other steroid oxidoreductases. This review presents an overview of the function and expression of both types of enzymes with emphasis on steroidogenic P450s. The final part of the review on regulation of steroidogenesis includes a description of the normal physiological fluctuations in the steroid output of adrenal cortex and gonads, and provides an analysis of the relative role of enzyme levels in the determination of these fluctuations. The repertoire of enzymes expressed in a steroidogenic cell matches the cell's capacity for the biosynthesis of specific steroids. Thus, steroidogenic capacity is regulated mainly by tissue and cell specific expression of enzymes, and not by selective activation or inhibition of enzymes from a larger repertoire. The quantitative capacity of steroidogenic cells for the biosynthesis of specific steroids is determined by the levels of steroidogenic enzymes. The major physiological variations in enzyme levels, are generally associated with parallel changes in gene expression. The level of expression of each steroidogenic enzyme varies in three characteristics: (a) tissue- and cell-specific expression, determined during tissue and cell differentiation; (b) basal expression, in the absence of trophic hormonal stimulation; and (c) hormonal signal regulated expression. Each of these three types of expression probably represent the functioning of distinct gene regulatory elements. In adult steroidogenic tissues, the levels of most of the cell- and tissue-specific steroidogenic enzymes depend mainly on trophic hormonal stimulation mediated by a complex network of signal transduction systems
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Antioxidant Protective Mechanisms against Reactive Oxygen Species (ROS) Generated by Mitochondrial P450 Systems in Steroidogenic Cells
No full textMitochondrial P450 type enzymes catalyze central steps in steroid biosynthesis, including cholesterol conversion to pregnenolone, 11beta and 18 hydroxylation in glucocorticoid and mineralocorticoid synthesis, C-27 hydroxylation of bile acids, and 1alpha and 24 hydroxylation of 25-OH-vitamin D. These monooxygenase reactions depend on electron transfer from NADPH via FAD adrenodoxin reductase and 2Fe-2S adrenodoxin. These systems can function as a futile NADPH oxidase, oxidizing NADPH in absence of substrate, and leak electrons via adrenodoxin and P450 to O(2), producing superoxide and other reactive oxygen species (ROS). The degree of uncoupling depends on the P450 and steroid substrate. Studies with purified proteins and overexpression in cultured cells show consistently that adrenodoxin, but not reductase, is responsible for ROS production that can lead to apoptosis. In the ovary and corpus luteum, antioxidant enzyme activities superoxide dismutase, catalase, and glutathione peroxidase parallel steroidogenesis. Antioxidant beta-carotene, alpha-tocopherol, and ascorbate can protect against oxidative damages of P450 systems. In testis Leydig cells, steroidogenesis is associated with aging of the steroidogenic capacity
Epithelial sodium channel (ENaC) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Full text linkThe 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 sodium channel (ENaC) in GtoPdb v.2025.3
Full text linkOverviewThe 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 [10, 49, 15, 24, 23]. In these epithelia, Na+ ions flow from the extracellular fluid into the cytoplasm of epithelial cells via ENaC and are then pumped out of the cytoplasm into the interstitial fluid by the Na+/K+ ATPase located on the basolateral membrane [43]. 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 [7]. Thus, ENaC has a central role in regulating ECF volume and blood pressure, primarily via its function in the kidney [44]. The expression of ENaC subunits, hence its activity, is regulated by the renin-angiotensin-aldosterone system, and other factors involved in electrolyte homeostasis [44, 33].The genetics of the hereditary systemic pseudohypoaldosteronism type-I revealed that the activity of ENaC is dependent on three subunits encoded by three genes [24, 12]. Within the protein superfamily that includes ENaC, the crystal structure of ASIC was determined first, revealing a trimeric structure with a large extracellular domain anchored in the membrane with a bundle of six TM helices (two TM helices/subunit) [3, 27]. The first 3D structure of human ENaC was determined by single-particle cryo-electron microscopy at a resolution of 3.7 Å [39]. A recent study improved the resolution to 3 Å [40]. These structures confirmed that ENaC has a 3D quaternary structure similar to ASIC. ENaC is assembled as a hetero-trimer with a clockwise order of α-γ-β subunit viewed from the top, as shown previously [13]. In contrast to ASIC1 which can assemble into a functional homotrimer, ENaC activity can be reconstituted fully only as a heterotrimer with an αβγ or a δβγ composition [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 [17]. 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 [17]. In contrast to ENaC, CFTR (ion transporter defective in cystic fibrosis) is located on the non-cilial cell surface [17]. 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 [49]. 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 [49]. Thus, ENaC function regulates the volume of fluid lining epithelia essential for mucociliary clearance of respiratory airways, transport of germ cells, fertilization, implantation, and cell migration [38, 17, 24]. Genes and PhylogenyIn the human genome, there are four homologous genes (SCNN1A, SCNN1B, SCNN1D, and SCNN1G) that encode four proteins, α-, β-, γ-, and δ-ENaC that may be involved in the assembly of ENaC [11, 35, 48, 54]. These four subunits share 23-34% sequence identity and <20% identity with ASIC subunits [24]. The genes coding for all four ENaC subunits are present in all bony vertebrates with the exception of ray-finned fish genomes that have lost all ENaC genes. The mouse genome has lost the gene SCNN1D that codes for δ-ENaC [19, 24, 24]. The α-, β-, and γ-ENaC genes are also present in jawless vertebrates (e.g., lampreys) and cartilaginous fishes (e.g., sharks) [24]. Examination of the methylation patterns of the 5\u27-flanking region of SCNN1A, SCNN1B, and SCNN1G genes in human cells showed an inverse correlation between gene expression and DNA methylation, suggesting epigenetic transcriptional control of ENaC genes [42]. Channel biogenesis, assembly and functionThe expression of ENaC subunits is regulated primarily by aldosterone and many additional extracellular and intracellular factors [44, 32, 41]. Most of the studies indicate that the expression of the three subunits is not coordinated [9]. However, the transport of the subunits to the membrane is dependent on three intact subunits. Even a missense mutation in one subunit reduces the concentration of assembled channels on the cell surface [16]. ENaC is a constitutively active channel, i.e., the flow of Na+ ions is not dependent on an activating factor. Hence, heterologous cells expressing ENaC (e.g., Xenopus oocytes), must be maintained in a solution that contains amiloride to keep ENaC inhibited. To measure ENaC activity, the bath solution is switched to a solution without amiloride. ENaC has two major states: 1) Open, and 2) Closed. The probability of ENaC being in the open state is called ENaC open probability (Po). ENaC activity is regulated by a diverse array of factors that exert their effects by modifying, directly or indirectly, two major parameters: 1) The density of ENaC in the membrane; and 2) The channel open probability [28, 30]. The Po of ENaC is greatly decreased by external Na+ and this response is called Na+ self-inhibition [50, 4, 26].An important aspect of ENaC regulation is that the α and the γ subunits have conserved serine protease cleavage sites in the extracellular segment [24]. Cleavage of these subunits by proteases such as furin and plasmin leads to the activation of ENaC [45, 31, 1].Diseases associated with ENaC mutationsMutations in any of the three genes (SCNN1A, SCNN1B, and SCNN1G) may cause partial or complete loss of ENaC activity, depending on the mutation [12, 21]. Such loss-of-function mutations are associated with a syndrome named "systemic" or "multi-system" autosomal recessive pseudohypoaldosteronism type I (PHA1B) [20, 12, 24, 17, 56, 47]. So far, no mutation has been found in the SCNN1D gene that causes PHA. PHA patients suffer from severe salt loss from all aldosterone target organs expressing ENaC, including kidney, sweat and salivary glands and respiratory tract. During infancy and early childhood, the severe electrolyte disturbances, dehydration and acidosis may require recurrent hospitalizations. The severity and frequency of salt-wasting episodes improve with age [22]. PHA1B is also associated with a dysfunctional female reproductive system [17, 6]. The carboxy-terminal of ENaC includes a short consensus sequence called the PY motif. Mutations in this motif in SCNN1B and SCNN1G are associated with Liddle syndrome, which is characterized by early-onset hypertension [5, 51]. The PY motif is recognized by Nedd4-2 that is a ubiquitin ligase. Thus, mutations in the PY motif reduce ubiquitylation of ENaC leading to the accumulation of ENaC in the membrane, consequently enhance the activity of ENaC [46].ENaC expression in tumorsThe observation that [Na+] is higher in many cancerous cells as compared to non-cancerous cells has led to the suggestion that enhanced expression of ENaC may be responsible for increased metastasis [34]. However, analysis of RNA sequencing data of ENaC-encoding genes, and clinical data of cervical cancer patients from The Cancer Genome Atlas showed a negative correlation with histologic grades of tumor [52]. Similarly, studies on breast cancer cells that altered α-ENaC levels by over-expression or siRNA-mediated knockdown showed that increased α-ENaC expression was associated with decreased breast cancer cell proliferation [55]. In contrast, analysis of RNA sequencing data from The Cancer Genome Atlas showed that high expression of SCNN1A was correlated with poor prognosis in patients with ovarian cancer [36]. These findings indicate that the association of ENaC levels with tumorigenesis varies depending on the tissue.COVID-19The surface of SARS-CoV-2 virions that cause COVID-19 is covered by many glycosylated S (spike) proteins. These S proteins bind to the membrane-bound angiotensin-converting enzyme 2 (ACE2) as a first step in the entry of the virion into the host cell. Viral entry into the cell is dependent on the cleavage of the S protein (at Arg-667/Ser-668) by a serine-protease. Anand et al. showed that this cleavage site has a sequence motif that is homologous to the furin cleavage site in α-ENaC [2]. A comprehensive review on the pathological consequences of COVID-19 suggests a role for ENaC in the early phases of COVID-19 infection in the respiratory tract epithelia [18]
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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