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

• Previous radioautographic experiments demonstrated that binding sites labeled by [3H]5-HT and [3H]LSD in rat brain were seen in all layers of CA1, CA4 and the dentate gyrus but not in fields CA2 and CA3 of the hippocampus [6].

Anatomical context of CA4

• Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1 and CA4 pyramidal cell layer relative to the corresponding brain regions of rats (n = 3) injected with bovine serum albumin (105 pmol), which per se was ineffective in all respects [7].
• By Western blot, CA-IV immunoreactive polypeptide was detected in the cultured cells and also in native rabbit and porcine ciliary epithelium [5].
• Concentrations of bovine carbonic anhydrase isozyme VI (CA-IV) in bovine serum, saliva, normal milk, colostrum, submandibular gland, liver, and mammary gland were determined [8].
• Western blots of detergent extracts of main pulmonary artery endothelial cell monolayers did not show increased expression of carbonic anhydrase IV (molecular mass = 52 kDa) after incubation under hypercarbic conditions [9].

Associations of CA4 with chemical compounds

• In addition, Cl(-) channel inhibitors decreased fluid transport by at most 16%, and inhibition of membrane-bound carbonic anhydrase IV by benzolamide or dextran-bound sulfonamide decreased fluid transport by at most 29% [10].

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