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Signal transduction in CHO-cells stably transfected with domain-selective forms of murine ACE

Item Type:Article
Title:Signal transduction in CHO-cells stably transfected with domain-selective forms of murine ACE
Creators Name:Sun, X., Rentzsch, B., Gong, M., Eichhorst, J., Pankow, K., Papsdorf, G., Maul, B., Bader, M. and Siems, W.E.
Abstract:Membrane-bound human angiotensin-converting enzyme (ACE) has been reported to initiate an intracellular signaling after interaction with substrates or inhibitors. Somatic ACE is known to contain two distinct, extracellular catalytic centers. We analyzed the signal transduction mechanisms in cells transfected with different forms of murine ACE (mACE) and investigated whether the two domains are similarly involved in these processes. For this purpose, CHO-cells were stably transfected with mACE or with its domain-selective mutants. Besides these modified cellular models human umbilical vein endothelial cells were used in this study. Signal transduction molecules like JNK and c-Jun were analyzed after activation of cells with several ACE-substrates and -inhibitors. ACE-targeting compounds like substrates, inhibitors, or even the ACE product angiotensin-II induce in mACE-expressing cells a signal transduction response. These processes are also evoked by partially inactivated forms of mACE and result finally in an enhanced cyclooxygenase-2 transcription. Surprisingly, also the membrane-bound ACE activity is influenced by ACE-targeted interventions. Our data suggest that the two catalytic domains of mACE do not function independently; but the signal transduction is influenced by a negative co-operativity of the two catalytic domains. This work underlines that ACE has indeed receptor-like properties which occur in a species-specific manner.
Keywords:ACE Domains, Angiotensin-Converting Enzyme, CHO Cells, c-Jun, HUVEC Cells, JNK, Animals, Mice, Cricetinae, Cricetulus
Source:Biological Chemistry
Publisher:de Gruyter
Page Range:235-244
Date:February 2010
Official Publication:https://doi.org/10.1515/BC.2010.020
PubMed:View item in PubMed

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