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https://www.readbyqxmd.com/read/28515172/cross-sex-transplantation-alters-gene-expression-and-enhances-inflammatory-response-in-the-transplanted-kidneys
#1
Lei Wang, Jiangping Song, Shaohui Wang, Jacentha Buggs, Rongjun Chen, Jie Zhang, Liqing Wang, Song Rong, Wenbin Li, Jin Wei, Ruisheng Liu
Kidney transplantation (KTX) is a life-saving procedure for patients with end-stage renal disease. Expression levels of many genes in kidney vary between males and females which may play an essential role in the sex differences in graft function. However, whether these differences are affected after cross-sex-KTX is unknown. In the present study, we assessed post-operative changes in genotype, function and inflammatory responses of the grafts in same-sex and cross-sex-KTX. Single kidney transplants were performed between same and different sex C57BL/6 mice paired into 4 combination groups: female donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male recipient (F/M); and male donor/female recipient (M/F)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28492512/aldosterone-and-mineralocorticoid-receptors-physiology-and-pathophysiology
#2
John W Funder
Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28481660/spx-101-is-a-novel-enac-targeted-therapeutic-for-cystic-fibrosis-that-restores-mucus-transport
#3
David W Scott, Matthew P Walker, Juliana Sesma, Bryant Wu, Timothy J Stuhlmiller, Juan R Sabater, William M Abraham, Timothy M Crowder, Dale J Christensen, Robert Tarran
RATIONALE: Cystic Fibrosis lung disease (CF) is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium which creates an osmotic gradient that pulls fluid out of the airway. Hyperactivation of ENaC contributes to reduced airway hydration causing mucus dehydration, decreased mucociliary clearance, and chronic bacterial infections...
May 8, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28480509/oxidized-low-density-lipoprotein-stimulates-epithelial-sodium-channels-in-endothelial-cells-of-mouse-thoracic-aorta
#4
Chen Liang, Qiu-Shi Wang, Xu Yang, Na Niu, Qing-Qing Hu, Bao-Long Zhang, Ming-Ming Wu, Chang-Jiang Yu, Xiao Chen, Bin-Lin Song, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Epithelial sodium channel (ENaC) is expressed in endothelial cells and acts as a negative modulator of vasodilation. Oxidized low-density lipoprotein (ox-LDL) is a key pathological factor in endothelial dysfunction. The present study is to examine the role of ENaC in ox-LDL-induced endothelial dysfunction and its associated signal transduction pathway. EXPERIMENTAL APPROACH: Patch-clamp techniques combined with pharmacological approaches were used to examine ENaC activity in the endothelial cells of split-open mouse thoracic aorta...
May 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28473772/lack-of-effects-of-metformin-and-aicar-chronic-infusion-on-the-development-of-hypertension-in-dahl-salt-sensitive-rats
#5
Tengis S Pavlov, Vladislav Levchenko, Daria V Ilatovskaya, Hui Li, Oleg Palygin, Nuria M Pastor-Soler, Kenneth R Hallows, Alexander Staruschenko
In the kidney, reabsorption via the epithelial sodium channel (ENaC) is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS) hypertension in Dahl SS rats. AMP-activated kinase (AMPK), playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP) in Dahl SS rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28468944/enac-activity-is-regulated-by-calpain-2-proteolysis-of-marcks-proteins
#6
Darrice S Montgomery, Ling Yu, Zinah M Ghazi, Tiffany L Thai, Otor Al-Khalili, He-Ping Ma, Douglas C Eaton, Abdel A Alli
We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca(2+)-dependent cysteine proteases involved in signal transduction. Here we examine the role of calpain-2 in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney...
May 3, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28463591/rab-gtpases-regulate-the-trafficking-of-channels-and-transporters-a-focus-on-cystic-fibrosis
#7
Carlos M Farinha, Paulo Matos
The amount of ion channels and transporters present at the plasma membrane is a crucial component of the overall regulation of ion transport. The number of channels present result from an intricate network of proteins that controls the late events of channel trafficking, such as endocytosis, recycling and targeting to lysosomal degradation. Small GTPases of the Rab family are key players in these processes thus contributing to regulation of fluid secretion and ion homeostasis. In epithelia, this involves mainly the balance between the chloride channel CFTR and the sodium channel ENaC, whose misfunction is a hallmark of cystic fibrosis - the commonest recessive disorder in Caucasians...
May 2, 2017: Small GTPases
https://www.readbyqxmd.com/read/28446807/increased-blood-pressure-in-nesfatin-nuclebindin-2-transgenic-mice
#8
Yusaku Mori, Hiroyuki Shimizu, Hideki Kushima, Munenori Hiromura, Michishige Terasaki, Michitaka Tanaka, Aya Osaki, Tsutomu Hirano
Nesfatin/nucleobindin-2 (nesf/NUCB2), a precursor of the anorexigenic protein nesfatin-1, is selectively expressed in the hypothalamic nuclei, which are central to the regulation of the autonomic nervous system. The present study sought to investigate the involvement of nesf/NUCB2 in the regulation of blood pressure and ingestive behavior, by using nesf/NUCB2-transgenic (Tg) mice. Blood pressure and heart rates were measured under conscious and unconscious conditions. Twenty-four-hour water intake and urine volume of male nesf/NUCB2-Tg mice and their littermates in metabolic cages were measured...
April 27, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#9
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28431985/quercetin-interferes-with-the-fluid-volume-and-receptivity-development-of-the-uterus-in-rats-during-the-peri-implantation-period
#10
Huma Shahzad, Nelli Giribabu, Kamarulzaman Karim, Normadiah Kassim, Sekaran Muniandy, Kilari Eswar Kumar, Naguib Salleh
HYPOTHESIS: Quercetin could induce changes to the fluid volume and receptivity development of the uterus during peri-implantation period. METHODS: Female rats were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning from day-1 pregnancy. Uterus was harvested at day-4 (following three days quercetin treatment) for morphological, ultra-structural, protein and mRNA expressional changes and plasma sex-steroid levels analyses. In another cohort of rats, implantation rate was determined at day-6 (following five days quercetin treatment)...
April 18, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28424211/connecting-tubule-glomerular-feedback-mediates-tubuloglomerular-feedback-resetting-post-unilateral-nephrectomy
#11
Sumit R Monu, Yilin Ren, J X Masjoan Juncos, Kristopher Kutskill, Hong Wang, Nitin Kumar, Edward L Peterson, Oscar A Carretero
Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (PGC) that can cause significant glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) Tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC)...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28409833/dietary-salt-blunts-vasodilation-by-stimulating-epithelial-sodium-channels-in-endothelial-cells-from-salt-sensitive-rats
#12
Zi-Rui Wang, Hui-Bin Liu, Ying-Ying Sun, Qing-Qing Hu, Yu-Xia Li, Wei-Wan Zheng, Chang-Jiang Yu, Xin-Yuan Li, Ming-Ming Wu, Bin-Lin Song, Jian-Jun Mu, Zu-Yi Yuan, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley (SD) rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. EXPERIMENTAL APPROACH: We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28409346/development-and-diseases-of-the-collecting-duct-system
#13
Lihe Chen, Paul J Higgins, Wenzheng Zhang
The collecting duct of the mammalian kidney is important for the regulation of extracellular volume, osmolarity, and pH. There are two major structurally and functionally distinct cell types: principal cells and intercalated cells. The former regulates Na(+) and water homeostasis, while the latter participates in acid-base homeostasis. In vivo lineage tracing using Cre recombinase or its derivatives such as CreGFP and CreER(T2) is a powerful new technique to identify stem/progenitor cells in their native environment and to decipher the origins of the tissue that they give rise to...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28405801/urine-exosomes-from-healthy-and-hypertensive-pregnancies-display-elevated-level-of-%C3%AE-subunit-and-cleaved-%C3%AE-and-%C3%AE-subunits-of-the-epithelial-sodium-channel-enac
#14
Maria R Nielsen, Britta Frederiksen-Møller, Rikke Zachar, Jan S Jørgensen, Mie R Hansen, Rikke Ydegaard, Per Svenningsen, Kristian Buhl, Boye L Jensen
Preeclampsia is characterized by hypertension, proteinuria, suppression of plasma renin-angiotensin-aldosterone, and impaired urine sodium excretion. Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and promote Na(+) reabsorption and urine K(+) loss. Plasma and urine was sampled from patients with preeclampsia, healthy pregnant controls and non-pregnant women, and from patients with nephrostomy catheters. Aldosterone concentration, urine plasminogen, and protein were determined...
April 12, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28386087/delivery-of-enac-sirna-to-epithelial-cells-mediated-by-a-targeted-nanocomplex-a-therapeutic-strategy-for-cystic-fibrosis
#15
Maria D I Manunta, Aristides D Tagalakis, Martin Attwood, Ahmad M Aldossary, Josephine L Barnes, Mustafa M Munye, Alexander Weng, Robin J McAnulty, Stephen L Hart
The inhibition of ENaC may have therapeutic potential in CF airways by reducing sodium hyperabsorption, restoring lung epithelial surface fluid levels, airway hydration and mucociliary function. The challenge has been to deliver siRNA to the lung with sufficient efficacy for a sustained therapeutic effect. We have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome (DOTMA/DOPE; L), an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28383056/involvement-of-epithelial-na-channel-in-the-elevated-myogenic-response-in-posterior-cerebral-arteries-from-spontaneously-hypertensive-rats
#16
Soo-Kyoung Choi, Soo-In Yeon, Youngin Kwon, Seonhee Byeon, Young-Ho Lee
Hypertension is characterized by increased peripheral vascular resistance which is related with elevated myogenic response. Recent findings have indicated that epithelial sodium channel (ENaC) is involved in mechanotransduction of the myogenic response. The purpose of this study was to investigate the involvement of ENaC in the elevated myogenic response of posterior cerebral arteries (PCAs) from spontaneously hypertensive rats (SHRs). Sixteen to eighteen weeks old male wistar kyoto rats (WKYs) and SHRs were used in this study...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28365586/enac-and-romk-activity-are-inhibited-in-the-dct2-cnt-of-tgwnk4-phaii-mice
#17
Chengbiao Zhang, Lijun Wang, Xiao-Tong Su, Junhui Zhang, Dao-Hong Lin, Wen-Hui Wang
Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4(PHAII)) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na(+) delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na(+) channel (ENaC) and renal outer medullary K(+) channel (ROMK or Kir4.1) are expressed in the late DCT and play an important role in mediating K(+) secretion, the aim of the present study is to test whether ROMK and ENaC activity in the DCT/CNT are also compromised in the mice expressing PHAII mutant Wnk4...
April 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28356292/responses-of-distal-nephron-na-transporters-to-acute-volume-depletion-and-hyperkalemia
#18
Gustavo Frindt, Lei Yang, Shinichi Uchida, Alan M Weinstein, Lawrence G Palmer
We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block Na+ transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (30 mg/kg) Na+ and K+ excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved γ-subunit) were detected...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28334404/calcium-homeostasis-modulator-1-like-currents-in-rat-fungiform-taste-cells-expressing-amiloride-sensitive-sodium-currents
#19
Albertino Bigiani
Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels...
May 1, 2017: Chemical Senses
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#20
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
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