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Publication : Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-γ2.

First Author  Mitterberger MC Year  2012
Journal  Exp Cell Res Volume  318
Issue  8 Pages  877-86
PubMed ID  22507175 Mgi Jnum  J:183923
Mgi Id  MGI:5319566 Doi  10.1016/j.yexcr.2012.02.011
Citation  Mitterberger MC, et al. (2012) Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-gamma2. Exp Cell Res 318(8):877-86
abstractText  Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO(2) have been proposed. CAIII expression is highly induced in adipogenesis and CAIII is the most abundant protein in adipose tissues. The function of CAIII in both preadipocytes and adipocytes is however unknown. In the present study we demonstrate that adipogenesis is greatly increased in mouse embryonic fibroblasts (MEFs) from CAIII knockout (KO) mice, as demonstrated by a greater than 10-fold increase in the induction of fatty acid-binding protein-4 (FABP4) and increased triglyceride formation in CAIII(-/-) MEFs compared with CAIII(+/+) cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) and CCAAT/enhancer binding protein-alpha. We found a considerable (approximately 1000-fold) increase in the PPARgamma2 expression in the CAIII(-/-) MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPARgamma2 and FABP4. When both CAIII and PPARgamma2 were knocked down, FABP4 was not induced. We conclude that down-regulation of CAIII in preadipocytes enhances adipogenesis and that CAIII is a regulator of adipogenic differentiation which acts at the level of PPARgamma2 gene expression.
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