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Control of cell cycle by metabolites of prostaglandin D2 through a non-cAMP mediated mechanismThe dehydration products of PGD2, 9-deoxy-9 prostaglandin D2(PGJ2), 9-deoxy-delta 9, delta 12, delta 13 dehydroprostaglandin D2 (delta 12 PGJ2), and PGA2 all contain an unsaturated cyclopentenone structure which is characteristic of prostaglandins which effectively inhibit cell growth. It has been suggested that the action of the inhibitory prostaglandins may be through a cAMP mechanism. In this study, we use S49 wild type (WT) and adenylate cyclase variant (cyc-) cells to show that PGD2 and PGJ2 are not acting via a cyclic AMP mechanism. First, the increase in cyclic AMP in wild type S-49 cells is not proportional to its effects on DNA synthesis. More importantly, when S-49 cyc- cells were exposed to PGJ2, the adenylate cyclase (cyc-) mutant had decreased DNA synthesis with no change in its nominal cAMP content. Short-term (2 hours or less) exposure of the cyc- cells to prostaglandin J2 caused an inhibition of DNA synthesis. PGJ2 caused cytolysis at high concentrations. Long-term exposure (>14 hrs) of the cells to PGJ2, delta 12PGJ2 or delta 12, delta 14PGJ2 caused a cell cycle arrest in G1 demonstrating a cell cycle specific mechanism of action for growth inhibition by naturally occurring biological products independent of cAMP.
Document ID
20040121490
Acquisition Source
Headquarters
Document Type
Reprint (Version printed in journal)
Authors
Hughes-Fulford, M.
(VA Medical Center San Francisco, CA, United States)
Fukushima, M.
Date Acquired
August 22, 2013
Publication Date
January 1, 1993
Publication Information
Publication: Life science advances. Experimental and clinical endocrinology : a journal of the Council of Scientific Research Integration
Volume: 12
ISSN: 0971-5053
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: NAGW-1244
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cell Biology
Non-NASA Center

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