Disease relevance of Car3

• Expression of CA III in rodent models of obesity [1].
• Protracted 60 min ischemia yielded equal amounts of both partially and completely (both sulfhydryls) modified CAIII due to irreversible oxidization [2].
• The physiological role of carbonic anhydrase III in slow-twitch skeletal muscle was investigated using isolated mouse soleus (N = 30) contracting once every 1.7 min for 75 min in Krebs-Henseleit solution gassed with either 95% oxygen - 5% carbon dioxide (normocapnia) or 90% oxygen - 10% carbon dioxide (hypercapnia) [3].

High impact information on Car3

• RNA blots demonstrate that CAIII messages can be detected in a variety of cell types but that high-level expression is limited to human fetal and adult skeletal muscle and to rodent slow skeletal muscle and liver [4].
• Previous reports have established the CAI and CAII isozyme genes to be closely linked on chromosome 8, and the assignment of the CAIII gene to the same chromosome raises the possibility that these genes may all be linked at a single complex locus [4].
• We have isolated a full-length representative of a CAIII mRNA transcript from an adult human muscle cDNA library, and we present the complete nucleotide sequence of this cDNA clone [4].
• They had normal amounts and distribution of fat, despite the fact that carbonic anhydrase III constitutes about 30% of the soluble protein in adipocytes [5].
• Carbonic anhydrase III has also been implicated in the response to oxidative stress [5].

Chemical compound and disease context of Car3

• Thus carbonic anhydrase III inhibition with sodium cyanate increased the effect of hypercapnia implying that carbonic anhydrase III assists in the regulation of free hydrogen ion concentration in slow-twitch skeletal muscle [3].

Biological context of Car3

• The amino acid sequences of two CNBr peptides were identical with portions of the mouse skeletal muscle carbonic anhydrase III (CAIII) sequence [6].
• Mapping of mouse carbonic anhydrase-3, Car-3: another locus in the homologous region of mouse chromosome 3 and human chromosome 8 [7].
• 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 [7].
• Nucleotide sequence and structure of the mouse carbonic anhydrase III gene [8].
• Expression of CAIII in the notochord is of interest in the context of skeletal myogenesis because the notochord is thought to play an important role in somite formation [9].

Anatomical context of Car3

• Compared with cultures maintained in the absence of insulin, 3T3 adipocytes maintained in the presence of insulin exhibited 65-90% lower concentrations of CA III [10].
• Protein and mRNA analyses show that CAIII is present at low levels in cultured myoblasts and is abundant in adult skeletal muscle and in liver [11].
• As the notochord forms the nucleus pulposus in fetal mice, CAIII mRNA levels remain very high [9].
• By two weeks post partum (p.p.), CAIII mRNAs are detected mainly in slow muscle fibers [9].
• In addition to the notochord, CAIII transcripts are detected prenatally in several other non-muscle tissues: in cells of the choroid plexus, endocardial cushion and ureter, and in adipocytes [9].

Associations of Car3 with chemical compounds

• Inhibition of the sulfonamide-sensitive activity had no effect on contractile and fatigue characteristics, whereas inhibition of the sulfonamide-resistant carbonic anhydrase III activity led to a significant increase in resistance to fatigue [12].
• Similarly, cultures maintained in a low bicarbonate/CO2 media (GibCO2-I medium containing 1 mM bicarbonate under an atmosphere of 100% humidified air) displayed 30-50% lower CA II and CA III concentrations [10].
• The high sensitivity of mucus CA to acetazolamide rules out its identity with cytosolic CAIII [13].
• When the active site residue Phe 198 in human CA III was replaced with Leu, measurement of catalysis showed that Glu 64 retained but Asp 64 lost its capacity to act as a proton shuttle [14].
• Maximal turnover rates for the hydration of CO2 and the depletion of 18O from CO2 catalyzed by carbonic anhydrase III (CA III) and carbonic anhydrase V (CA V) are limited by proton transfer involving zinc-bound water or hydroxide in the active site [14].

Other interactions of Car3

• Copper loading of normal mice also decreased hepatic CAIIIA mRNA, suggesting that the decrease in CAIII mRNA in the tx mouse liver is a secondary consequence of the high copper levels in the liver [6].
• Carbonic anhydrase III occurred alone in some and with CA II in other sites but was often absent from CA-II-containing types of cells [15].
• Importantly, Car1, Car3, and Car13 showed very high expression levels in certain tissues as compared to the other CAs, suggesting that these low activity isozymes may also participate in physiological processes other than CA catalysis and high expression levels are required to fulfil their functions in the body [16].
• 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 [10].
• One potential muscle marker, carbonic anhydrase III, is expressed in early mesoderm and subsequently in the notochord, similarly to the Brachyury gene [17].

Analytical, diagnostic and therapeutic context of Car3

• Car-3 has been assigned to band 3A2 by in situ hybridization [7].
• Immunoblotting with an antibody developed against rat carbonic anhydrase III showed that it was also specific for this 29-kDa peptide, which presumably is the mouse carbonic anhydrase III [12].
• These MAbs demonstrated potential for use in the development of an immunoassay for CAIII, and for investigating the biology of skeletal muscle injury in vivo [18].
• The rat clones were used to estimate mRNA from liver and muscle on Northern blots and showed that the sexual dimorphism of CAIII in rat liver relates to a difference in mRNA levels [19].
• Conditionally immortalized muscle precursor cells were transfected with a gene targeting construct designed to replace the MyHCIIB promoter with that for the carbonic anhydrase III gene (CAIII), which is highly expressed in slow muscle [20].

References