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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To help understand the biological functions of carbonic anhydrase-related proteins (CA-RPs VIII, X, and XI), we obtained cDNA clones of murine CA-RPs X and XI and studied the tissue distribution of all three CA-RPs and their developmental expression in the murine embryonic brain. The amino acid sequences of murine CA-RPs are highly conserved with their human homologues, indicating a fundamental biological role of CA-RPs. Among a panel of vital organs, the strongest mRNA expression of all three CA-RPs was consistently observed in the brain. Immunohistochemical analysis revealed the expression of all three CA-RPs in the neural cell body and neurites. CA-RP X was also observed in the myelin sheath, as demonstrated using the shiverer demyelinated mouse. In murine embryos, CA-RP VIII and X messages first appeared in the middle of the gestation period, while the CA-RP XI message was seen at an early gestational stage and expressed to a lesser extent as gestation progressed. All CA-RPs were expressed in the neuroprogenitor cells in the subventricular area and subsequently detected in the neural cells migrating to the cortex. Although the exact function of CA-RPs is still undefined, these findings suggest an important role of CA-RPs in the CNS.
Brain Res Mol Brain Res 2002 Dec 30
PMID:cDNA cloning and developmental expression of murine carbonic anhydrase-related proteins VIII, X, and XI. 1253 30

In this study, the rapid (within 2 h) effects of acute anaemia on blood gas and acid-base status, as well as cardiorespiratory variables, were examined in brown bullhead (Ameiurus nebulosus). Anaemia was induced by blood withdrawal coupled to volume replacement with saline. Lowering haematocrit from the control value of 23.5+/-1.0% (mean+/-S.E.M.; N=37) to 5.9+/-0.3% (N=37) resulted in a significant increase (by 2.63+/-0.51 torr; N=7) in arterial CO(2) tension (PaCO(2)) over the subsequent 2-h period in the absence of a change in arterial O(2) tension (PaO(2)). Treatment with bovine carbonic anhydrase (CA) reduced the extent of the PaCO(2) increase to the point where it was not statistically significant. In both control and CA-treated fish, arterial pH decreased during acute anaemia; the acidosis was of mixed respiratory and metabolic origin in control fish and primarily metabolic in CA-treated fish. Inducing anaemia caused increases in both cardiac output (V*b) and heart rate that were similar in control and CA-treated fish. Experimental elevation of V*b equivalent to that observed during anaemia, but in the absence of lowered haematocrit, increased PaCO(2) significantly by 1.49+/-0.74 to 1.64+/-0.78 torr (N=5) without affecting PaO(2). These findings suggest that CO(2) excretion in bullhead, as in rainbow trout, is effectively diffusion-limited, and that approximately half of the increase in PaCO(2) measured during the initial 2 h of anaemia results from the impact of increased blood flow (hence decreased gill transit time) in a diffusion-limited system.
Comp Biochem Physiol A Mol Integr Physiol 2003 May
PMID:Apparent diffusion limitations on branchial CO2 transfer are revealed by severe experimental anaemia in brown bullhead (Ameiurus nebulosus). 1272 53

To search for the biochemical parameters involved in calcium and carbonate transport during crystal formation and biomineralisation in nacreous molluscs, the carbonic anhydrase activity, the levels of calciotropic hormones in hemolymph and in tissues and the circulating concentration of calcium were measured in pearl oysters (Pinctada margaritifera) during a phase of active growth. Activity of carbonic anhydrase in gill tissue increased linearly with age of the animals, while no age variation in activity was noted for the mantle. The circulating level of total calcium increased during the growth of the animals. Calciotropic hormones were radioimmunoassayed in gill, mantle and hemolymph. Only a calcitonin-gene related peptide (CGRP) could be detected and its concentration decreased as a function of growth, both in hemolymph and mantle. No variation in CGRP concentration with age was observed in gill tissue. Our data demonstrate that carbonic anhydrase and a molecule biologically and immunologically related to CGRP are involved during growth of the animals. In addition, this study shows the presence of three main calcium compartments, gill, hemolymph and mantle, involved in the biomineralisation process.
Comp Biochem Physiol A Mol Integr Physiol 2003 Jun
PMID:Biomineralisation markers during a phase of active growth in Pinctada margaritifera. 1278 27

A sufficient availability of the bicarbonate anion is required to allow a normal process of glucose-stimulated insulin release. Thus, both the removal of extracellular bicarbonate and the inhibition of carbonic anhydrase by acetazolamide suppress the insulinotropic action of glucose. In the present study, a comparable situation is documented in rat parotid cells. Thus, the absence of extracellular bicarbonate is shown to decrease by about 50% basal alpha-amylase secretion, as well as carbamylcholine- and isoproterenol-stimulated alpha-amylase output, without suppressing the enhancing action of the two agents. It is proposed, therefore, that the HCO3-anion participates in the secretory sequence at sites distal to the identification of secretagogues in both endocrine and exocrine cells.
Int J Mol Med 2003 Aug
PMID:Alteration of alpha-amylase secretion from rat parotid cells in the absence of extracellular bicarbonate. 1285 17

High ambient Ca2+ at bone resorption sites have been implicated to play an important role in the regulation of bone remodeling. The present study was performed to clarify the mode of high extracellular Ca2+ (Ca2+(e))-induced modulation of osteoclastogenesis and the expression of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG), thereby to define its role in osteoclast formation. Mouse bone marrow cells were cocultured with osteoblastic cells in the absence or presence of osteoclastogenic factors such as 1,25-dihydroxyvitaminD3 (1,25-(OH)2vitD3)and macrophage colony-stimulating factor/soluble RANKL. Ca2+ concentration in media (1.8 mM) was adjusted to 3, 5, 7 or 10 mM. Osteoclast formation was confirmed by the appearance of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and the expression of osteoclast phenotypic markers (calcitonin receptor, vitronectin receptor, cathepsin K, matrix metalloproteinase-9, carbonic anhydrase 2). High Ca2+(e) alone significantly stimulated osteoclast formation in a dose-dependent manner. However, in the presence of highly osteoclastogenic factors, high Ca2+(e) significantly inhibited osteoclastogenesis. High Ca2+(e) alone continuously up-regulated RANKL expression while only transiently increased OPG expression. However, in the presence of 1,25-(OH)(2)vitD(3), high Ca2+(e) did not change the 1,25-(OH)2vitD3-induced RANKL expression while increased OPG expression. Taken together, these findings suggest that high Ca2+(e) alone increase osteoclastogenesis but inhibit in the presence of other osteoclastogenic factors. In addition, high CaCa2+(e)-induced osteoclastogenesis may be mediated by osteoblasts via up-regulation of RANKL expression. Meanwhile up-regulated OPG might participate in the inhibitory effect of high Ca2+(e) on 1,25-(OH)2vitD3-induced osteoclastogenesis.
Exp Mol Med 2003 Jun 30
PMID:High extracellular Ca2+ alone stimulates osteoclast formation but inhibits in the presence of other osteoclastogenic factors. 1285 15

Thomas H. Maren studied carbonic anhydrase (CA) for half a century, venturing into all aspects of this powerful enzyme from active site chemistry to clinical medicine. He was a keen proponent of comparative physiology to illuminate basic principles of the chemistry and biology of CA and spent 47 summers at the Mt. Desert Island Biological Laboratory (MDIBL) studying many non-mammalian species. Following the venerable strategy of selecting the right creature to explore a particular question, Maren derived important insights into the role of CA in ion transport, acid-base regulation and gas exchange. Using the fact that tissue CAs are expressed variably in different species, and that these animals differ in temperature, acid-base status and metabolic rate, he defined the contributions of un-catalyzed and catalyzed CO(2) reactions in many physiological processes. Often this strategy simplified a problem and offered answers not easily obtainable in mammals. As examples, he verified the primary role of HCO(3)(-) as lead ion in CSF formation in fish and extended this to mammals. Using marine fish whose kidneys have very little CA, he uncovered mechanisms of acid-base transfer independent of CA that help to explain why CA inhibition does not lead to total bicarbonate depletion.
Comp Biochem Physiol A Mol Integr Physiol 2003 Oct
PMID:A comparative approach to carbonic anhydrase: the work of Thomas H. Maren. 1451 43

The euryhaline green crab, Carcinus maenas, is a relatively strong osmotic and ionic regulator, being able to maintain its hemolymph osmolality as much as 300 mOsm higher than that in the medium when the crab is acclimated to low salinity. It makes the transition from osmoconformity to osmoregulation at a critical salinity of 26 ppt, and new acclimated concentrations of hemolymph osmotic and ionic constituents are reached within 12 h after transfer to low salinity. One of the central features of this transition is an 8-fold induction of the enzyme carbonic anhydrase (CA) in the gills. This induction occurs primarily in the cytoplasmic pool of CA in the posterior, ion-transporting gills, although the membrane-associated fraction of CA also shows some induction in response to low salinity. Inhibition of branchial CA activity with acetazolamide (Az) has no effect in crabs acclimated to 32 ppt but causes a depression in hemolymph osmotic and ionic concentrations in crabs acclimated to 10 ppt. The salinity-sensitive nature of the cytoplasmic CA pool and the sensitivity of hemolymph osmotic/ionic regulation to Az confirm the enzyme's role in ion transport and regulation in this species. CA induction is a result of gene activation, as evidenced by an increase in CA mRNA at 24 h after transfer to low salinity and an increase in protein-specific CA activity immediately following at 48 h post-transfer. CA gene expression appears to be under inhibitory control by an as-yet unidentified repressor substance found in the major endocrine complex of the crab, the eyestalk.
Comp Biochem Physiol A Mol Integr Physiol 2003 Oct
PMID:Salinity-mediated carbonic anhydrase induction in the gills of the euryhaline green crab, Carcinus maenas. 1451 44

The different isozymes of carbonic anhydrase (CA) have been the subject of intensive study in mammals, but there is still much to be learned about the early evolution of this enzyme in vertebrates. Erythrocyte CA plays an essential role in the respiratory processes of most vertebrates and is probably the most well studied CA isozyme. The available evidence indicates that there has been a progressive increase in the efficiency of erythrocyte CA during the early evolution of vertebrates. There also appears to be a substantial increase in erythrocyte CA activity during development in some species. At the present time, however, the selective pressures that may be influencing the properties of erythrocyte CA during vertebrate evolution and development have not been clearly determined. When the available molecular sequence information is examined, it is evident that the erythrocyte CAs of early vertebrates have active sites that are more similar to those of mammalian CA VII and II, rather than CA I. We can now also begin to examine the phylogenetic relationships between the different rbc CAs in vertebrates, but more CA sequence information is clearly required from different groups of vertebrates before we have a complete picture of the molecular evolution of erythrocyte CA.
Comp Biochem Physiol A Mol Integr Physiol 2003 Oct
PMID:Comparative physiology and molecular evolution of carbonic anhydrase in the erythrocytes of early vertebrates. 1451 45

We show here that luminal mucus from the colon and the stomach of guinea pigs, mice and humans exhibits substantial carbonic anhydrase (CA) activity, by which the velocity of the CO(2) hydration reaction is accelerated 1000-2000-fold, approximately 1/10 of what is found in the red cell. Although this CA shares several properties with CA II, studies with CA II-deficient mice show that gastrointestinal mucus CA is not affected in these animals and thus does not appear to be CA II. We speculate that the mucus layer covering the luminal surface of gastrointestinal epithelium can, due to the presence of CA, maintain a normal tissue pCO(2) in the epithelium, even when the pCO(2) values in the lumen are much higher, as is known for stomach and colon. To test this hypothesis, we have developed a mathematical model which describes (a) diffusion of CO(2) and HCO(3)(-) across the mucus layer and (b) H(+) transport mediated by continuous secretion of mucus, which due to its high H(+) buffer capacity transports H(+) by convection towards the lumen. The model predicts that continuous transport of the reaction products of CO(2) towards the lumen, by diffusion and convection, protects the epithelium against high CO(2) partial pressures in the lumen.
Comp Biochem Physiol A Mol Integr Physiol 2003 Oct
PMID:Carbonic anhydrase in the gastrointestinal mucus of mammals--possible protective role against carbon dioxide. 1451 47

Current understanding of chloride cells (CCs) is briefly reviewed with emphasis on molecular aspects of their channels, transporters and regulators. Seawater-type and freshwater-type CCs have been identified based on their shape, location and response to different ionic conditions. Among the freshwater-type CCs, subpopulations are emerging that are implicated in the uptake of Na(+), Cl(-) and Ca(2+), respectively, and can be distinguished by their shape of apical crypt and affinity for lectins. The major function of the seawater CC is transcellular secretion of Cl(-), which is accomplished by four major channels and transporters: (1). CFTR Cl(-) channel, (2). Na(+),K(+)-ATPase, (3). Na(+)/K(+)/2Cl(-) cotransporter and (4). a K(+) channel. The first three components have been cloned and characterized, but concerning the K(+) channel that is essential for the continued generation of the driving force by Na(+),K(+)-ATPase, only one candidate is identified. Although controversial, freshwater CCs seem to perform the uptake of Na(+), Cl(-) and Ca(2+) in a manner analogous to but slightly different from that seen in the absorptive epithelia of mammalian kidney and intestine since freshwater CCs face larger concentration gradients than ordinary epithelial cells. The components involved in these processes are beginning to be cloned, but their CC localization remains to be established definitively. The most important yet controversial issue is the mechanism of Na(+) uptake. Two models have been postulated: (i). the original one involves amiloride-sensitive electroneutral Na(+)/H(+) exchanger (NHE) with the driving force generated by Na(+),K(+)-ATPase and carbonic anhydrase (CA) and (ii). the current model suggests that Na(+) uptake occurs through an amiloride-sensitive epithelial sodium channel (ENaC) electrogenically coupled to H(+)-ATPase. While fish ENaC remains to be identified by molecular cloning and database mining, fish NHE has been cloned and shown to be highly expressed on the apical membrane of CCs, reviving the original model. The CC is also involved in acid-base regulation. Analysis using Osorezan dace (Tribolodon hakonensis) living in a pH 3.5 lake demonstrated marked inductions of Na(+),K(+)-ATPase, CA-II, NHE3, Na(+)/HCO(3)(-) cotransporter-1 and aquaporin-3 in the CCs on acidification, leading to a working hypothesis for the mechanism of Na(+) retention and acid-base regulation.
Comp Biochem Physiol B Biochem Mol Biol 2003 Dec
PMID:Molecular biology of major components of chloride cells. 1466 88


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