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CA4  -  carbonic anhydrase IV

Bos taurus

 
 
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Disease relevance of CA4

  • Murine B-16 melanoma and P-388 leukemia were also highly sensitive to CA-4 in vitro with an identical IC50 value of 0.0007 micrograms/mL for continuous drug exposure for 8 days [1].
  • In colony forming assays using 10% fetal bovine serum, CA-4 was inhibitory in 27/40 human ovary cancers with a mean IC50 of 3.18 micrograms/mL for a 1-hour exposure (n = 35 specimens) and 0.27 microgramf1p4for a continuous exposure to CA-4 for 11-14 days (n = 5 specimens) [1].
 

High impact information on CA4

  • The alpha 2 transcript is enriched in the dentate gyrus and CA4/CA3 regions of the hippocampus [2].
  • When expressed in COS cells, the cDNA produced a 43- to 44-kDa protein in membranes that had around one-sixth the CA activity of membranes from COS cells transfected with the same vector expressing bovine CA IV [3].
  • The Ki values for 11 sulfonamides with CA IV were measured and in all cases showed less binding (averaging 17-fold) than to CA II [4].
  • Data are compatible with the proposed role of CA IV in physiological events, i.e., HCO3- formation and secretion at one cell border and H+ separation and excretion at the other [4].
  • In contrast, membrane-associated CA was SDS resistant, a characteristic of the CA-IV isozyme [5].
 

Biological context of CA4

 

Anatomical context of CA4

 

Associations of CA4 with chemical compounds

 

Analytical, diagnostic and therapeutic context of CA4

  • Using the same reversed-phase HPLC technique as developed for paclitaxel, CA-4 was shown to bind to serum proteins (> or = 30,000 mw) > 99% and to albumin approximately 70% [1].
  • The presence of membrane-bound carbonic anhydrase (CAIV) was confirmed by immunoblotting [11].

References

  1. Antitumor activity of combretastatin-A4 phosphate, a natural product tubulin inhibitor. Dorr, R.T., Dvorakova, K., Snead, K., Alberts, D.S., Salmon, S.E., Pettit, G.R. Investigational new drugs. (1996) [Pubmed]
  2. Distinct GABAA receptor alpha subunit mRNAs show differential patterns of expression in bovine brain. Wisden, W., Morris, B.J., Darlison, M.G., Hunt, S.P., Barnard, E.A. Neuron (1988) [Pubmed]
  3. Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal localization of a carbonic anhydrase gene that is overexpressed in some renal cell cancers. Türeci, O., Sahin, U., Vollmar, E., Siemer, S., Göttert, E., Seitz, G., Parkkila, A.K., Shah, G.N., Grubb, J.H., Pfreundschuh, M., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Chemical properties of carbonic anhydrase IV, the membrane-bound enzyme. Maren, T.H., Wynns, G.C., Wistrand, P.J. Mol. Pharmacol. (1993) [Pubmed]
  5. Membrane-associated carbonic anhydrase in cultured rabbit nonpigmented ciliary epithelium. Wu, Q., Delamere, N.A., Pierce, W. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  6. Regional differences in binding of [3H]LSD and [3H]5-HT in calf hippocampal slices revealed by radioautography and rapid filtration studies. Meibach, R.C., Beck, S.G., Maayani, S., Green, J.P. Brain Res. (1984) [Pubmed]
  7. N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors mediate seizures and CA1 hippocampal damage induced by dendrotoxin-K in rats. Bagetta, G., Iannone, M., Palma, E., Nisticò, G., Dolly, J.O. Neuroscience (1996) [Pubmed]
  8. Measurement of Carbonic Anhydrase Isozyme VI (CA-VI) in Bovine Sera, Saliva, Milk and Tissues. Nishita, T., Tanaka, Y., Wada, Y., Murakami, M., Kasuya, T., Ichihara, N., Matsui, K., Asari, M. Vet. Res. Commun. (2007) [Pubmed]
  9. Effect of hypercarbia on surface proteins of cultured bovine endothelial cells. Rounds, S., Piggott, D., Dawicki, D.D., Farber, H.W. Am. J. Physiol. (1997) [Pubmed]
  10. Immunocytochemical localization of Na+-HCO3- cotransporters and carbonic anhydrase dependence of fluid transport in corneal endothelial cells. Diecke, F.P., Wen, Q., Sanchez, J.M., Kuang, K., Fischbarg, J. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  11. Apical and basolateral CO2-HCO3- permeability in cultured bovine corneal endothelial cells. Bonanno, J.A., Guan, Y., Jelamskii, S., Kang, X.J. Am. J. Physiol. (1999) [Pubmed]
 
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