Carbonic anhydrase II expression pattern in mouse embryonic and fetal heart

Vuillemin, Mauricette; Pexieder, Tomáš

doi:10.1007/s004290050046

Cited by 9 publications

(4 citation statements)

References 51 publications

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“…NHE1 and AE3 in the myocardium are functionally linked by carbonic anhydrase (CA), which catalyses the hydration of CO 2 : CO 2 + H 2 O ↔ H 2 CO 3 ↔ H + + HCO 3 − to produce both the H + and HCO 3 − substrates for transport by NHE1 and AE3 (Pastorekova et al 2004). CAII is a near-ubiquitous cytosolic isoform, which was previously thought not to be expressed in adult rat cardiomyocytes (Geers et al 1992) but was identified in embryonic and fetal hearts (Vuillemin & Pexieder, 1997). However, recent studies using DNA microarray analysis of adult human heart has identified CAII mRNA in these tissues (http://cardiogenomics.med.harvard.edu/home (2005)).…”

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confidence: 99%

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

Álvarez¹,

Johnson²,

Sowah³

et al. 2007

The Journal of Physiology

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Hypertrophic cardiomyocyte growth contributes substantially to the progression of heart failure. Activation of the plasma membrane Na + -H + exchanger (NHE1) and Cl − -HCO 3 − exchanger (AE3) has emerged as a central point in the hypertrophic cascade. Both NHE1 and AE3 bind carbonic anhydrase (CA), which activates their transport flux, by providing H + and HCO 3 − , their respective transport substrates. We examined the contribution of CA activity to the hypertrophic response of cultured neonatal and adult rodent cardiomyocytes. Phenylephrine (PE) increased cell size by 37 ± 2% and increased expression of the hypertrophic marker, atrial natriuretic factor mRNA, twofold in cultured neonatal rat cardiomyocytes. Cell size was also increased in adult cardiomyocytes subjected to angiotensin II or PE treatment. These effects were associated with increased expression of cytosolic CAII protein and the membrane-anchored isoform, CAIV. The membrane-permeant CA inhibitor, 6-ethoxyzolamide (ETZ), both prevented and reversed PE-induced hypertrophy in a concentration-dependent manner in neonate cardiomyocytes (IC 50 = 18 µM). ETZ and the related CA inhibitor methazolamide prevented hypertrophy in adult cardiomyocytes. In addition, ETZ inhibited transport activity of NHE1 and the AE isoform, AE3, with respective EC 50 values of 1.2 ± 0.3 µM and 2.7 ± 0.3 µM. PE significantly increased neonatal cardiomyocyte Ca 2+ transient frequency from 0.33 ± 0.4 Hz to 0.77 ± 0.04 Hz following 24 h treatment; these Ca 2+ -handling abnormalities were completely prevented by ETZ (0.28 ± 0.07 Hz). Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype.

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confidence: 99%

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

Álvarez¹,

Johnson²,

Sowah³

et al. 2007

The Journal of Physiology

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“…CAII, a near-ubiquitous cytosolic isoform, is expressed in mouse embryonic and fetal heart, and adult mouse heart [13,22]. We examined the expression of CAII in mouse and human hearts, by immunoblotting.…”

Section: Resultsmentioning

confidence: 99%

Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart

Álvarez

Quon

Mullen

et al. 2013

BMC Cardiovasc Disord

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BackgroundCarbonic anhydrase enzymes (CA) catalyze the reversible hydration of carbon dioxide to bicarbonate in mammalian cells. Trans-membrane transport of CA-produced bicarbonate contributes significantly to cellular pH regulation. A body of evidence implicates pH-regulatory processes in the hypertrophic growth pathway characteristic of hearts as they fail. In particular, Na+/H+ exchange (NHE) activation is pro-hypertrophic and CA activity activates NHE. Recently Cardrase (6-ethoxyzolamide), a CA inhibitor, was found to prevent and revert agonist-stimulated cardiac hypertrophy (CH) in cultured cardiomyocytes. Our goal thus was to determine whether hypertrophied human hearts have altered expression of CA isoforms.MethodsWe measured CA expression in hypertrophied human hearts to begin to examine the role of carbonic anhydrase in progression of human heart failure. Ventricular biopsies were obtained from patients undergoing cardiac surgery (CS, n = 14), or heart transplantation (HT, n = 13). CS patients presented mild/moderate concentric left ventricular hypertrophy and normal right ventricles, with preserved ventricular function; ejection fractions were ~60%. Conversely, HT patients with failing hearts presented CH or ventricular dilation accompanied by ventricular dysfunction and EF values of 20%. Non-hypertrophic, non-dilated ventricular samples served as controls.ResultsExpression of atrial and brain natriuretic peptide (ANP and BNP) were markers of CH. Hypertrophic ventricles presented increased expression of CAII, CAIV, ANP, and BNP, mRNA levels, which increased in failing hearts, measured by quantitative real-time PCR. CAII, CAIV, and ANP protein expression also increased approximately two-fold in hypertrophic/dilated ventricles.ConclusionsThese results, combined with in vitro data that CA inhibition prevents and reverts CH, suggest that increased carbonic anhydrase expression is a prognostic molecular marker of cardiac hypertrophy.

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“…Demonstration of embryonic mRNA and protein expression of several CA genes make it possible to propose an alternative model for VSD formation involving CA inhibition (Carter et al, 1990; Edwards et al, 1992). Interestingly, CA expression was frequently detected in developing heart (Gay et al, 1981; Schreiner et al, 1981; Lyons et al, 1991; Lakkis et al, 1997) including the interventricular septum, the site of VSDs (Vuillemin and Pexieder, 1997).…”

Section: Introductionmentioning

confidence: 99%

Rat embryos express transcripts for cyclooxygenase‐1 and carbonic anhydrase‐4, but not for cyclooxygenase‐2, during organogenesis

Streck

Kumpf

Ozolins̆

et al. 2003

Birth Defects Research Pt B

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BACKGROUND: Acetylsalicylic acid (ASA) is a rat teratogen, and exposures on gestational days (GDs) 9 and 10 induce diaphragm, cardiac, and midline defects. ASA inhibits members of the cyclooxygenase (COX) family and potentially members of the carbonic anhydrase (CA) family. The objective of this study was to determine whether the mRNA developmental expression pattern for any COX or CA isoform was consistent with a model in which ASA teratogenicity is mediated through direct interaction with one of these enzymes within embryos or within the adjacent ectoplacental cone (EPC) or yolk sac. METHODS: Staged embryos, over a range (GD 9.5–12) that included ASA‐sensitive and ASA‐insensitive stages of organogenesis, were assayed for COX and CA mRNA levels by three techniques: microarrays; in situ hybridization quantitated by a micro‐imager; and quantitative reverse transcription polymerase chain reaction. ASA‐ and vehicle‐treated embryos also were compared to determine whether inhibition led to upregulated COX or CA mRNA expression. RESULTS: COX‐2 mRNA was undetectable in embryos throughout organogenesis by any assay (although it was abundant in EPC). In contrast, COX‐1 mRNA was moderately abundant in embryos throughout organogenesis. One CA isoform, CA‐4, demonstrated developmentally regulated embryonic mRNA expression that coincided with ASA sensitivity. ASA exposure failed to induce upregulation of any of these mRNAs. CONCLUSIONS: Although ASA may affect the embryo indirectly through interaction with COX‐2 within EPC, failure to detect embryonic COX‐2 mRNA argues against COX‐2 functioning as a direct mediator of ASA teratogenic activity in induction of cardiac, diaphragm, and midline defects. Correlation of COX‐1 and CA‐4 expression with ASA sensitivity suggested that embryonic COX‐1 and possibly CA‐4 are much more likely candidates for mediators of ASA developmental toxicity. Birth Defects Research (Part B) 68:57–69, 2003. © 2003 Wiley‐Liss, Inc.

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Carbonic anhydrase II expression pattern in mouse embryonic and fetal heart

Cited by 9 publications

References 51 publications

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart

Rat embryos express transcripts for cyclooxygenase‐1 and carbonic anhydrase‐4, but not for cyclooxygenase‐2, during organogenesis

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