Abstract:
:Incubation of cultured bovine pulmonary artery endothelial cells with 200 microM of 3-isobutyl-1-methylxanthine (IBMX) for 24 hr produced a five- to tenfold increase in cellular angiotensin converting enzyme activity (ACE) above that of untreated control cells. A lesser increase was observed in medium ACE. Other methylxanthines produced a similar, but less marked, effect. The elevation of ACE seemed to require de novo protein synthesis since it was reduced by 0.1 microgram/ml cycloheximide. Elevation of cellular cAMP was detected at 30 min after introduction of IBMX, then rapidly returned to control levels at 1 hour, while elevation in cellular ACE at 24 hr required contact with IBMX for at least 2 hr. Hence, the transient elevation in cAMP is unlikely to be the cause of the elevation of ACE. Phorbol ester and synthetic diacyl glycerol OAG, activators of protein kinase C, did not elevate ACE. Indomethacin, at a concentration known to inhibit cyclooxygenase activity, had no effect on the elevation of ACE. The elevation of ACE by IBMX was not affected by the calcium channel blocker verapamil or the calcium chelator EGTA. In contrast, the effect of IBMX was totally abolished by the calmodulin inhibitors trifluoperazine and calmidazolium. The data show that IBMX elevates endothelial cell ACE and suggest that the elevation is mediated by a calcium-calmodulin complex. The studies demonstrate a novel effect of methylxanthines on endothelial cells in culture.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Dasarathy Y,Fanburg BLdoi
10.1002/jcp.1041370122subject
Has Abstractpub_date
1988-10-01 00:00:00pages
179-84issue
1eissn
0021-9541issn
1097-4652journal_volume
137pub_type
杂志文章abstract::The ultimate destiny of a cell to undergo division, differentiation, survival, and death results from an intricate balance between multiple regulators including oncogenes, tumor suppressor genes, and cell cycle associated proteins. Deregulation of the cell cycle machinery switches the phenotype from a normal cell to a...
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