Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epithelial Ca(2+) channel (ECaC), which is exclusively expressed in 1,25-dihydroxyvitamin D(3)-responsive tissues, i.e., kidney, intestine, and placenta, is postulated to constitute the initial step in the process of transcellular Ca(2+) transport. To strengthen this postulated function, the present study compares the segmental and cellular distribution of ECaC and the other Ca(2+) transport proteins known to be involved in transcellular Ca(2+) transport. In rabbit kidney, ECaC mRNA and protein expression were primarily present in the connecting tubule. Immunopositive staining for the ECaC protein was exclusively found at the apical domain of this tubular segment. Importantly, ECaC completely colocalized with calbindin-D(28K), Na(+)-Ca(2+) exchanger (NCX), and plasma membrane Ca(2+) -ATPase (PMCA). A minority of cells along the distal tubule lacked immunopositive staining for ECaC and the other Ca(2+) transporting proteins. These negative cells were identified as intercalated cells. In intestine, ECaC was present in a thin layer along the apical membrane of the duodenal villus tip, whereas the crypt and goblet cells were negative. Again, a complete colocalization was observed between ECaC, calbindin-D(9K), and PMCA. In contrast to the kidney, NCX could not be detected in duodenum. The present finding that ECaC completely colocalizes with the Ca(2+) transport proteins in the connecting tubule and duodenum, together with its apical localization, further substantiates the postulated function of ECaC as the gatekeeper of active Ca(2+) (re)absorption.
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PMID:Localization of the epithelial Ca(2+) channel in rabbit kidney and intestine. 1086 72

Transepithelial transport of calcium involves uptake at the apical membrane, movement across the cell, and extrusion at the basolateral membrane. Active vitamin D metabolites regulate the latter two processes by induction of calbindin D and the plasma membrane ATPase (calcium pump), respectively. The expression of calbindin D and the calcium pump declines with age in parallel with transepithelial calcium transport. The apical uptake of calcium is thought to be mediated by the recently cloned calcium channels-CaT1 (or ECaC2, TRPV6) and CaT2 (or ECaC1, TRPV5). The purpose of these studies was to determine whether there were age-related changes in intestinal calcium channel regulation and to identify the dietary factors responsible for their regulation. Young (2 months) and adult (12 months) rats were fed either a high calcium or low calcium diet for 4 weeks. The low calcium diet significantly increased duodenal CaT1 and CaT2 mRNA levels in both age groups, but the levels in the adult were less than half that of the young. The changes in calcium channel expression with age and diet were significantly correlated with duodenal calcium transport and with calbindin D levels. To elucidate the relative roles of serum 1,25(OH)2D3 and calcium in the regulation of calcium channel expression, young rats were fed diets containing varying amounts of calcium and vitamin D. Dietary vitamin D or exogenous 1,25(OH)2D3 more than doubled CaT1 mRNA levels, and this regulation was independent of dietary or serum calcium. These findings suggest that the apical calcium channels, along with calbindin and the calcium pump, may play a role in intestinal calcium transport and its modulation by age, dietary calcium, and 1,25(OH)2D3.
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PMID:Effect of age, vitamin D, and calcium on the regulation of rat intestinal epithelial calcium channels. 1582 Feb 16

The purpose of the present work was to study the possible role of the epithelial Ca(2+) channel (ECaC) in the Ca(2+) uptake mechanism in developing zebrafish (Danio rerio). With rapid amplification of cDNA ends, full-length cDNA encoding the ECaC of zebrafish (zECaC) was cloned and sequenced. The cloned zECaC was 2,578 bp in length and encoded a protein of 709 amino acids that showed up to 73% identity with previously described vertebrate ECaCs. The zECaC was found to be expressed in all tissues examined and began to be expressed in the skin covering the yolk sac of embryos at 24 h postfertilization (hpf). zECaC-expressing cells expanded to cover the skin of the entire yolk sac after embryonic development and began to occur in the gill filaments at 96 hpf, and thereafter zECaC-expressing cells rapidly increased in both gills and yolk sac skin. Corresponding to ECaC expression profile, the Ca(2+) influx and content began to increase at 36-72 hpf. Incubating zebrafish embryos in low-Ca(2+) (0.02 mM) freshwater caused upregulation of the whole body Ca(2+) influx and zECaC expression in both gills and skin. Colocalization of zECaC mRNA and the Na(+)-K(+)-ATPase alpha-subunit (a marker for mitochondria-rich cells) indicated that only a portion of the mitochondria-rich cells expressed zECaC mRNA. These results suggest that the zECaC plays a key role in Ca(2+) absorption in developing zebrafish.
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PMID:Epithelial Ca(2+) channel expression and Ca(2+) uptake in developing zebrafish. 1594 67

The molting cycle of the freshwater crayfish, Procambarus clarkii, has been used as a model to study the cellular physiology and molecular biology of Ca "supply" proteins that effect transcellular vectorial Ca(2+) movement to achieve organismal Ca homeostasis. Specifically, periods of net Ca(2+) influx (postmolt) have been compared with periods of net Ca(2+) balance (intermolt). The broader goal is to understand the paradox facing epithelial cells of maintaining low cytosolic Ca(2+)in the face of mass Ca(2+)transit across epithelial cells. This mini-review compares mRNA and protein expression profiles for a series of proteins that are of strategic importance in effecting transcellular Ca(2+) flux in a selected epithelium, the antennal gland (kidney analog) specifically during apical to basolateral Ca(2+) conveyance. Target proteins were selected as representative of key "stages" in the transcellular transfer of Ca(2+): import (epithelial Ca(2+) channel, ECaC); storage (sarco/endoplasmic reticulum Ca(2+) ATPase, SERCA); buffering (sarcoplasmic Ca(2+) binding protein, SCP); and export (plasma membrane Ca(2+) ATPase, PMCA and Na(+)/Ca(2+) exchanger, NCX). The purpose of this review is to assess coordination of expression of these target proteins at times of high Ca(2+) demand (premolt and postmolt) compared to low Ca demand (intermolt) as a function of cellular location (apical vs. basolateral; endomembranes vs. plasma membranes) and relative abundance within different regions of the antennal gland. Understanding the spatiotemporal regulation of Ca(2+) handling proteins involved in transcellular transport is fundamental to investigating their endocrine regulation.
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PMID:Paradox of epithelial cell calcium homeostasis during vectorial transfer in crayfish kidney. 1753 39

The ion regulation mechanisms of fishes have been recently studied in zebrafish (Danio rerio), a stenohaline species. However, recent advances using this organism are not necessarily applicable to euryhaline fishes. The euryhaline species medaka (Oryzias latipes), which, like zebrafish, is genetically well categorized and amenable to molecular manipulation, was proposed as an alternative model for studying osmoregulation during acclimation to different salinities. To establish its suitability as an alternative, the present study was conducted to (1) identify different types of ionocytes in the embryonic skin and (2) analyze gene expressions of the transporters during seawater acclimation. Double/triple in situ hybridization and/or immunocytochemistry revealed that freshwater (FW) medaka contain three types of ionocyte: (1) Na(+)/H(+) exchanger 3 (NHE3) cells with apical NHE3 and basolateral Na(+)-K(+)-2Cl(-) cotransporter (NKCC), Na(+)-K(+)-ATPase (NKA) and anion exchanger (AE); (2) Na(+)-Cl(-) cotransporter (NCC) cells with apical NCC and basolateral H(+)-ATPase; and (3) epithelial Ca(2+) channel (ECaC) cells [presumed accessory (AC) cells] with apical ECaC. On the other hand, seawater (SW) medaka has a single predominant ionocyte type, which possesses apical cystic fibrosis transmembrane conductance regulator (CFTR) and NHE3 and basolateral NKCC and NKA and is accompanied by smaller AC cells that express lower levels of basolateral NKA. Reciprocal gene expressions of decreased NHE3, AE, NCC and ECaC and increased CFTR and NKCC in medaka gills during SW were revealed by quantative PCR analysis.
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PMID:A new model for fish ion regulation: identification of ionocytes in freshwater- and seawater-acclimated medaka (Oryzias latipes). 2484 48