| First Author | Mardones P | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1840 |
| Issue | 6 | Pages | 1765-70 |
| PubMed ID | 24361611 | Mgi Jnum | J:210863 |
| Mgi Id | MGI:5571990 | Doi | 10.1016/j.bbagen.2013.12.015 |
| Citation | Mardones P, et al. (2014) Cyclic AMP and alkaline pH downregulate carbonic anhydrase 2 in mouse fibroblasts. Biochim Biophys Acta 1840(6):1765-70 |
| abstractText | BACKGROUND: The hydration of CO2 catalyzed by the ubiquitous carbonic anhydrase 2 (Ca2) is central for bicarbonate transport, bone metabolism and acid-base homeostasis in metazoans. There is evidence that in some tissues Ca2 expression can be acutely induced by cAMP, whereas in other cell types it is unresponsive to cAMP-mediated transcriptional activation. METHODS: We isolated fibroblasts from wild type and mice lacking the ubiquitous chloride/bicarbonate exchanger (Ae2a,b(-/-) mice). In these cells the regulation of carbonic anhydrase 2 by cAMP was studied. RESULTS: We show that Ca2 expression is strongly inhibited by chronic incubation with dibutyryl-cAMP, forskolin or alkaline pH in cultured mouse fibroblasts. Furthermore, fibroblasts obtained from anion exchanger 2 deficient (Ae2a,b(-/-)) mice, which display intracellular alkalosis and increased cAMP production, express less than 10% of control Ca2 mRNA and protein. Surprisingly, inhibition of the bicarbonate-sensitive soluble adenylyl cyclase (sAC) was found to reduce CA2 expression instead of increasing it. CONCLUSIONS: CA2 expression is strongly regulated by intracellular pH and by cAMP, suggesting a role for soluble adenylyl cyclase. Regulation occurs in opposite directions which may be explained by an incoherent feedforward loop consisting of activation by pCREB and repression by ICER. |
