Disease relevance of CA2

• Carbonic anhydrase II (CAII) is highly expressed in the osteoclast, where it is involved in the process of extracellular acidification required for bone resorption [1].
• Structural similarities between the animal and cyanobacterial enzymes extend to the levels of antigenicity, as the Anabaena protein cross-reacts with antisera derived against chicken CAII [2].
• At day 13/14, progressive developmental hypoxia causes the release of norepinephrine and erythroid beta-adrenergic receptor stimulation initiates the coordinate induction of adaptive key events of erythroid differentiation like carbonic anhydrase (CAII) and 2,3-biphosphoglycerate synthesis [3].

High impact information on CA2

• We have previously shown that 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], a steroid hormone that regulates the differentiation of macrophages and osteoclasts, induces the expression of CAII mRNA and protein in avian bone marrow cells [1].
• 1 alpha,25-dihydroxyvitamin D3 regulates the transcription of carbonic anhydrase II mRNA in avian myelomonocytes [1].
• To determine whether this regulation occurred at the gene level, we have studied the effects of 1,25(OH)2D3 on CAII expression in a transformed myelomonocytic avian cell line (BM2) [1].
• Thus, 1,25(OH)2D3 modulates CAII gene expression at the transcriptional level, and this effect does not require de novo synthesis of other gene products [1].
• These results suggest that activation of the CAII gene occurs early in the differentiation events triggered by vitamin D3 in myelomonocytic cells [1].

Chemical compound and disease context of CA2

• In late chick embryos, coordinate activation of red cell carbonic anhydrase II (CAII) and 2,3-diphosphoglycerate (2,3-DPG) synthesis is initiated by hypoxia [4].

Biological context of CA2

• The complete nucleotide sequence of the coding region of the chicken carbonic anhydrase II (CA II) gene has been determined from clones isolated from a chicken genomic library [5].
• Utilization of the second polyadenylation signal at the 3' end of the chicken carbonic anhydrase II gene [6].
• The number of introns as well as five of the six intron locations are conserved between the chicken and mouse CA II genes [5].
• Measurements of CA II RNA levels in various cell types suggest that CA II RNA increases in parallel with globin RNA during erythropoiesis and exists only at low levels, if at all, in non-erythroid cells [5].
• A novel carbonic anhydrase II mRNA isolated from mature chicken testis displays a TATA box and other promoter sequences in a leader 5' untranslated region not present in somatic tissues [7].

Anatomical context of CA2

• However, the 5' untranslated region (UTR) of the testis CAII mRNA is larger than the corresponding somatic sequence [7].
• The 5' UTR contains a leader sequence not present in the CAII mRNA isolated from erythroid cells or chick retina [7].
• The longest cDNA clone encodes all but the first three amino acids of CA-II, and the encoded sequence generally agrees with published fragments of CA-II sequence from chick red blood cells [8].
• These results suggest that 1,25(OH)2D3 regulates the level at which myelomonocytic precursors express CAII, an enzyme that is involved in the function of the mature osteoclast [9].
• To test whether 1,25(OH)2D3 could induce the differentiation of myelomonocytic precursors toward osteoclasts rather than macrophages, we analyzed its effects on the expression of CAII in bone marrow cultures containing precursors common to both cell types [9].

Associations of CA2 with chemical compounds

• E9 T4 administration decreased corneal thickness by E12; increased DIO3, THRB, and CA2 expressions 5- to 20-fold; decreased KSPG core protein genes and galactose sulfotransferase CHST1 expressions 2-fold; and reduced KS disulfated/monosulfated disaccharide (DSD/MSD) ratios [10].
• These effects were completely blocked by actinomycin D, and nuclear run-on analysis confirmed that 1,25(OH)2D3 increased the rate of CAII gene transcription [1].
• In contrast, induction of CAII mRNA expression was not affected by inhibition of protein synthesis with cycloheximide, and no significant changes in mRNA stability were seen [1].
• Thyroxine affects expression of KSPG-related genes, the carbonic anhydrase II gene, and KS sulfation in the embryonic chicken cornea [10].
• Differential regulation of the carbonic anhydrase II gene expression by hormonal nuclear receptors in monocytic cells: identification of the retinoic acid response element [11].

Other interactions of CA2

• Two of the cDNAs, corresponding to brain creatine kinase and carbonic anhydrase-II RNAs, had previously been cloned, while the products encoded by the three remaining RNAs were tentatively identified as the chicken counterparts of mammalian cytosolic aldehyde dehydrogenase, stathmin and a member of the fatty acid binding protein family [12].
• Immunohistochemical colocalization of HKalpha(2c) with carbonic anhydrase II, the Cl(-)/HCO exchanger AE1, and HKalpha(1) indicated that both type A and type B intercalated cells possessed intense apical HKalpha(2c) immunoreactivity, whereas principal cells and connecting segment cells had only a thin apical band of HKalpha(2c) [13].
• To investigate the cellular distribution of carbonic anhydrase by an independent technique, we have examined the chick brain by in situ hybridization to detect mRNA from the carbonic anhydrase-II gene, using as controls the actin and vimentin genes [14].

Analytical, diagnostic and therapeutic context of CA2

• By Western blot analysis, the CA2 and CA3 fusion proteins were found to react with CAV-infected chicken sera [15].
• Moreover, in the second half of the flock's reproductive life, the effect of using ejaculates of young roosters (CA2) in artificial insemination (AI) on the above parameters of fertility was estimated [16].
• Carbonic anhydrase-II messenger RNA in neurons and glia of chick brain: mapping by in situ hybridization [14].
• CA-II expression was measured by immunohistochemistry and radioimmunoassay during development, and CA-II mRNA was quantified by Northern blot and densitometric scanning and localized by in situ hybridization [17].

References