A Single Copy of Carbonic anhydrase 2 Restores Wild-type Circadian Period to Carbonic Anhydrase II-Deficient Mice

2006 ◽  
Vol 36 (2) ◽  
pp. 301-308 ◽  
Author(s):  
Kari L. Kernek ◽  
James A. Trofatter ◽  
Aimee R. Mayeda ◽  
Debomoy K. Lahiri ◽  
John R. Hofstetter
Keyword(s):  
Carbonic Anhydrase ◽  
Single Copy ◽  
Carbonic Anhydrase Ii ◽  
Circadian Period ◽  
Wild Type ◽  
Deficient Mice

Altered Circadian Period of Locomotor Activity in Carbonic Anhydrase II-Deficient Mice

1999 ◽  
Vol 30 (5) ◽  
pp. 517-528 ◽  
Author(s):  
J.R. Hofstetter ◽  
K.L. Gifford ◽  
J.A. Trofatter ◽  
A.R. Mayeda
Keyword(s):  
Locomotor Activity ◽  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Circadian Period ◽  
Deficient Mice

Oligodendrocytes express a normal phenotype in carbonic anhydrase II-deficient mice

1989 ◽  
Vol 23 (2) ◽  
pp. 180-190 ◽  
Author(s):  
M. S. Ghandour ◽  
R. P. Skoff ◽  
P. J. Venta ◽  
R. E. Tashian
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Normal Phenotype ◽  
Deficient Mice

scholarly journals Decreased Expression of Slc26a4 (Pendrin) and Slc26a7 in the Kidneys of Carbonic Anhydrase II-Deficient Mice

2008 ◽  
Vol 21 (1-3) ◽  
pp. 095-108 ◽  
Author(s):  
Xuming Sun ◽  
Manoocher Soleimani ◽  
Snezana Petrovic
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Deficient Mice

Carbonic anhydrase II promotes cardiomyocyte hypertrophy

2012 ◽  
Vol 90 (12) ◽  
pp. 1599-1610 ◽  
Author(s):  
Brittany F. Brown ◽  
Anita Quon ◽  
Jason R.B. Dyck ◽  
Joseph R. Casey
Keyword(s):  
Carbonic Anhydrase ◽  
Ventricular Myocytes ◽  
Dominant Negative ◽  
Neonatal Rat ◽  
Carbonic Anhydrase Ii ◽  
Cardiomyocyte Hypertrophy ◽  
Wild Type ◽  
Over Expression ◽  
Pathological Cardiac Hypertrophy ◽  
Neonatal Rat Ventricular Myocytes

Pathological cardiac hypertrophy, the maladaptive remodelling of the myocardium, often progresses to heart failure. The sodium–proton exchanger (NHE1) and chloride–bicarbonate exchanger (AE3) have been implicated as important in the hypertrophic cascade. Carbonic anhydrase II (CAII) provides substrates for these transporters (protons and bicarbonate, respectively). CAII physically interacts with NHE1 and AE3, enhancing their respective ion transport activities by increasing the concentration of substrate at their transport sites. Earlier studies found that a broad-spectrum carbonic anhydrase inhibitor prevented cardiomyocyte hypertrophy (CH), suggesting that carbonic anhydrase is important in the development of hypertrophy. Here we investigated whether cytosolic CAII was the CA isoform involved in hypertrophy. Neonatal rat ventricular myocytes (NRVMs) were transduced with recombinant adenoviral constructs to over-express wild-type or catalytically inactive CAII (CAII-V143Y). Over-expression of wild-type CAII in NRVMs did not affect CH development. In contrast, CAII-V143Y over-expression suppressed the response to hypertrophic stimuli, suggesting that CAII-V143Y behaves in a dominant negative fashion over endogenous CAII to suppress hypertrophy. We also examined CAII-deficient (Car2) mice, whose hearts exhibit physiological hypertrophy without any decrease in cardiac function. Moreover, cardiomyocytes from Car2 mice do not respond to prohypertrophic stimulation. Together, these findings support a role of CAII in promoting CH.

Regulation of the human NBC3 Na+/HCO3− cotransporter by carbonic anhydrase II and PKA

2004 ◽  
Vol 286 (6) ◽  
pp. C1423-C1433 ◽  
Author(s):  
Frederick B. Loiselle ◽  
Patricio E. Morgan ◽  
Bernardo V. Alvarez ◽  
Joseph R. Casey
Keyword(s):  
Carbonic Anhydrase ◽  
Recovery Rate ◽  
Dominant Negative ◽  
Carbonic Anhydrase Ii ◽  
Transport Activity ◽  
Wild Type ◽  
Hek 293 ◽  
Transfected Cells ◽  
293 Cells ◽  
Optimal Function

Human NBC3 is an electroneutral Na+/HCO3− cotransporter expressed in heart, skeletal muscle, and kidney in which it plays an important role in HCO3− metabolism. Cytosolic enzyme carbonic anhydrase II (CAII) catalyzes the reaction CO2 + H2O ⇆ HCO3− + H+ in many tissues. We investigated whether NBC3, like some Cl−/HCO3− exchange proteins, could bind CAII and whether PKA could regulate NBC3 activity through modulation of CAII binding. CAII bound the COOH-terminal domain of NBC3 (NBC3Ct) with Kd = 101 nM; the interaction was stronger at acid pH. Cotransfection of HEK-293 cells with NBC3 and CAII recruited CAII to the plasma membrane. Mutagenesis of consensus CAII binding sites revealed that the D1135-D1136 region of NBC3 is essential for CAII/NBC3 interaction and for optimal function, because the NBC3 D1135N/D1136N retained only 29 ± 22% of wild-type activity. Coexpression of the functionally dominant-negative CAII mutant V143Y with NBC3 or addition of 100 μM 8-bromoadenosine to NBC3 transfected cells reduced intracellular pH (pHi) recovery rate by 31 ± 3, or 38 ± 7%, respectively, relative to untreated NBC3 transfected cells. The effects were additive, together decreasing the pHi recovery rate by 69 ± 12%, suggesting that PKA reduces transport activity by a mechanism independently of CAII. Measurements of PKA-dependent phosphorylation by mass spectroscopy and labeling with [γ-32P]ATP showed that NBC3Ct was not a PKA substrate. These results demonstrate that NBC3 and CAII interact to maximize the HCO3− transport rate. Although PKA decreased NBC3 transport activity, it did so independently of the NBC3/CAII interaction and did not involve phosphorylation of NBC3Ct.

8 DECREASED OSTEOBLAST ACTIVITY IN CARBONIC ANHYDRASE II DEFICIENT MICE CAUSES OSTEOPOROTIC BONE

2004 ◽  
Vol 52 (Suppl 1) ◽  
pp. S80.3-S80
Author(s):  
D. S. Margolis ◽  
D. Kim ◽  
J. A. Szivek ◽  
L. Lai ◽  
G. Kastis ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ii ◽  
Osteoporotic Bone ◽  
Osteoblast Activity ◽  
Deficient Mice

scholarly journals Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy.

1998 ◽  
Vol 101 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
L W Lai ◽  
D M Chan ◽  
R P Erickson ◽  
S J Hsu ◽  
Y H Lien
Keyword(s):  
Gene Therapy ◽  
Carbonic Anhydrase ◽  
Renal Tubular Acidosis ◽  
Carbonic Anhydrase Ii ◽  
Renal Tubular ◽  
Deficient Mice

scholarly journals Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3

2015 ◽  
Vol 309 (4) ◽  
pp. F383-F392 ◽  
Author(s):  
Devishree Krishnan ◽  
Lei Liu ◽  
Shane A. Wiebe ◽  
Joseph R. Casey ◽  
Emmanuelle Cordat ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Intracellular Ph ◽  
Solid Phase ◽  
Carbonic Anhydrase Ii ◽  
Proximity Ligation Assay ◽  
Physical Interaction ◽  
Proximal Tubule Cell ◽  
Wild Type ◽  
Sodium Proton Exchanger

Two-thirds of sodium filtered by the renal glomerulus is reabsorbed from the proximal tubule via a sodium/proton exchanger isoform 3 (NHE3)-dependent mechanism. Since sodium and bicarbonate reabsorption are coupled, we postulated that the molecules involved in their reabsorption [NHE3 and carbonic anhydrase II (CAII)] might physically and functionally interact. Consistent with this, CAII and NHE3 were closely associated in a renal proximal tubular cell culture model as revealed by a proximity ligation assay. Direct physical interaction was confirmed in solid-phase binding assays with immobilized CAII and C-terminal NHE3 glutathione- S-transferase fusion constructs. To assess the effect of CAII on NHE3 function, we expressed NHE3 in a proximal tubule cell line and measured NHE3 activity as the rate of intracellular pH recovery, following an acid load. NHE3-expressing cells had a significantly greater rate of intracellular pH recovery than controls. Inhibition of endogenous CAII activity with acetazolamide significantly decreased NHE3 activity, indicating that CAII activates NHE3. To ascertain whether CAII binding per se activates NHE3, we expressed NHE3 with wild-type CAII, a catalytically inactive CAII mutant (CAII-V143Y), or a mutant unable to bind other transporters (CAII-HEX). NHE3 activity increased upon wild-type CAII coexpression, but not in the presence of the CAII V143Y or HEX mutant. Together these studies support an association between CAII and NHE3 that alters the transporter's activity.

Sign in / Sign up

Export Citation Format

Share Document