Disease relevance of Car1

• Direct RNA sequence analysis of the 5' nontranslated regions of CAI mRNA from mouse colon and mouse erythroleukemia cells demonstrated tissue specificity in the lengths and sequences of CAI transcripts [1].
• Chronic metabolic acidosis (CMA) in the rabbit upregulates carbonic anhydrase (CA) IV in the proximal convoluted tubule (PCT) [2].
• The carbonic anhydrase V produced by a vector containing the full coding sequence, which includes a possible NH2-terminal mitochondrial targeting signal, was proteolytically processed by E. coli and contained several amino-terminal ends [3].
• In flurothyl-induced seizures, CA deficient mice displayed longer latencies to the onset of both clonic and tonic-clonic seizures [4].
• Decrease in oligodendrocyte carbonic anhydrase activity preceding myelin degeneration in cuprizone induced demyelination [5].

Psychiatry related information on Car1

• However, when the mice were primed by a loud sound during the critical period and retested for audiogenic seizures again at age 1.5 months, the CA deficient mice displayed a significantly lower incidence of seizures [4].
• Correlation between effects of acute acetazolamide administration to mice on electroshock seizure threshold and maximal electroshock seizure pattern, and on carbonic anhydrase activity in subcellular fractions of brain [6].

High impact information on Car1

• The results also demonstrate an early decrease in transcription for carbonic anhydrase form I, which precedes decreases in transcription for glyceraldehyde phosphate dehydrogenase and rRNA genes [7].
• Functionally, inhibition of carbonic anhydrase activity led to the enhancement of recovery from DSS-induced acute colitis by directly stimulating CEC proliferation [8].
• Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9 [9].
• BACKGROUND & AIMS: Carbonic anhydrase (CA) IX is a highly active enzyme with adhesion capacity that is functionally implicated in acid-base balance and intercellular communication [9].
• They displayed a mixed cystic-papillary phenotype strongly positive for carbonic anhydrase activity [10].

Chemical compound and disease context of Car1

• In contrast, two other types of inhibitors of bone resorption in vitro, the carbonic anhydrase inhibitor acetazolamide (10 microM) and the aminobisphosphonate AHPrBP (10 microM), significantly inhibited cholera toxin-stimulated bone resorption [11].
• Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of increasing the toxicity of sodium salicylate in mice [12].
• It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis increases the concentration of salicylate in the brain [12].
• Bone resorption induced by parathyroid hormone and dibutyryl cyclic AMP: role of carbonic anhydrase [13].
• These results support the concepts that PTH-induced bone resorption requires the action of osteoclastic carbonic anhydrase and that the action of PTH on bone is mediated, in part, by the action of cyclic AMP [13].

Biological context of Car1

• Carbonic anhydrase (CA) II is the major CA isozyme in the brain, where it participates in acid-base homeostasis, fluid transport, and myelin synthesis [14].
• Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II [14].
• We identified a PstI restriction fragment length polymorphism between Mus spretus and Mus mus domesticus and, by using an interspecific backcross, showed that Car-3 is 2.4 +/- 1.7% SE from both Car-1 and Car-2, calculating genetic distance as percentage recombination [15].
• Evolution of mammalian carbonic anhydrase loci by tanden duplication: close linkage of Car-1 and Car-2 to the centromere region of chromosome 3 of the mouse [16].
• CONCLUSION: Membrane-bound CA isozymes IX and XII are expressed in various tissues during mouse organogenesis [17].

Anatomical context of Car1

• We compared the CA isozymes in brain and spinal cord fractions, as well as in purified myelin, between CA(II)D and control mice [14].
• The function of cytosolic carbonic anhydrase (CA) isozyme II is largely unknown in skeletal muscle [18].
• Carbonic anhydrase content varied among genera in liver and pancreas and between mouse species and strains in salivary glands and kidney [19].
• Carbonic anhydrase (CA) was examined in two adipocyte cell lines, 3T3-L1 and 3T3-F442A [20].
• Carbonic anhydrase (CA) III was demonstrated immunocytochemically in epithelium in some regions of salivary gland ducts, colon, bronchi, and male genital tract and in adipocytes, in addition to skeletal muscle and liver where the isozyme was previously localized [19].

Associations of Car1 with chemical compounds

• Because the regulation by pH and bicarbonate/CO2 may be relatively selective for CA in adipocytes, a simple method for reducing the concentration/activity of CA in 3T3 adipocytes is described that may be a useful tool for studies on the physiological role of the enzyme [20].
• The mechanism by which animals develop tolerance to the antiepileptic effects of the carbonic anhydrase (CA) inhibitor, acetazolamide, was explored using a quantitative immunocytochemical method [21].
• Carbonic anhydrase II-deficient mice offer a possibility to study the localization along the nephron of membrane-associated carbonic anhydrase (CA) activity without interference from the cytoplasmic enzyme [22].
• However, 60% of the total carbonic anhydrase activity in the mouse was of the sulfonamide-sensitive type and, therefore, not related to carbonic anhydrase III [23].
• Inhibition of CA (methazolamide, 25 mg/kg) led in all groups to equivalent increments of urine pH, urine flow, and HCO3-, Na+, and K+ excretion [24].

Physical interactions of Car1

• In Car-2(0) mouse colonic mucosa, total CA activity was reduced 80% and cytosolic CA I and membrane-bound CA IV activities were not increased [25].

Co-localisations of Car1

• In the oligodendrocytes acetyl-CoA carboxylase was colocalized with carbonic anhydrase, and fatty acid synthase was immunostained in the same cell-type [26].

Regulatory relationships of Car1

• By comparing normal mice with CA II-deficient mice, we were able to study membrane-bound CA without influence from the ubiquitous cytoplasmic CA II [27].
• The role of carbonic anhydrase in bone resorption induced by parathyroid hormone (PTH) and dibutyryl cyclic AMP (DBcAMP) was studied using an in vitro neonatal mouse half-calvarial culture system [13].

Other interactions of Car1

• CA(II)D resulted in a much lower total CA specific activity in all tissues examined but in higher CA IV specific activities in soluble and membrane-associated fractions and pure myelin [14].
• Both CA III and non-CA III activities, measured by 18O mass spectrometry, were present in 3T3-L1 and 3T3-F442A adipocytes; however, no CA activity was detected in 3T3 preadipocytes of either line [20].
• BACKGROUND: Of the thirteen active carbonic anhydrase (CA) isozymes, CA IX and XII have been linked to carcinogenesis [17].
• Striated ducts in guinea pig, but not mouse salivary glands, stained darker for CA and appeared accordingly to function more actively in ion transport compared with excretory ducts [19].
• CAI transcripts in the colon were found to initiate just upstream of the erythroid exon 2 of the CAI gene region sequence [1].

Analytical, diagnostic and therapeutic context of Car1

• With immunocytochemistry, we have determined distribution of sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) and of three isoenzymes of carbonic anhydrase (CA) and have shown absence of the chloride channel, Band 3 protein, in the genital tract of female rodents [28].
• Double immunofluorescence staining showed CA in myelinated tracts and oligodendrocytes in the cerebellum of the normal but not the CA II-deficient mice, and also in astrocytes in the cerebral cortex of the normal mice but not the mutants [29].
• Because these results implied that CA V, the mitochondrial isoform of carbonic anhydrase, might be present in adipocytes, CA V levels were measured by immunoblotting [30].
• A cDNA encoding the mouse carbonic anhydrase V gene was isolated by reverse transcription and polymerase chain reaction from BALB/c mouse liver mRNA [3].
• A rabbit polyclonal antibody directed against mouse erythrocyte carbonic anhydrase II was employed to localize carbonic anhydrase, II by light and electron microscopy by an indirect immunoperoxidase method [31].

References