Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-纬2

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• 作者：Maria C. Mitterberger^a ; Geumsoo Kim^b ; Ursula Rostek^a ; Rodney L. Levine^b ; Werner Zwerschke^a ; ^{werner.zwerschke@oeaw.ac.at}
• 关键词：ARE ; antioxidant response elements ; CAIII ; Carbonic anhydrase III ; C/EBP伪 ; CCAAT/enhancer binding protein-伪 ; FABP4 ; fatty acid-binding protein-4 ; GSH ; glutathione ; IBMX ; 3-Isobutyl-1-methylxanthin ; KO ; knockout ; MEF ; mouse embryonic fibroblasts ; NRF2 ; N
• 刊名：Experimental Cell Research
• 出版年：2012
• 期刊代码：292_00144827
• 类别：med
• 出版时间：1 May, 2012
• 卷：318
• 期：8
• 页码：877-886
• 文件大小：1000 K

摘要

Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO₂ 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^{鈭?鈭?/sup> MEFs compared with CAIII+/+ cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-纬2 (PPAR纬2) and CCAAT/enhancer binding protein-伪. We found a considerable (approximately 1000-fold) increase in the PPAR纬2 expression in the CAIII鈭?鈭?/sup> MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPAR纬2 and FABP4. When both CAIII and PPAR纬2 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 PPAR纬2 gene expression.}