Document Detail


Phospholipase A2 has a role in proliferation but not in differentiation of HL-60 cells.
MedLine Citation:
PMID:  9060998     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of phospholipase A2 (PLA2) and its metabolite arachidonic acid (AA) in the proliferation and differentiation of HL-60 cells was investigated. Addition of either 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or retinoic acid (RA) to HL-60 cells for 2 h inhibited PMA-stimulated PLA2 activity measured by [3H]AA release. The inhibitor of PLA2 activity, p-bromophenacyl bromide (BPB), significantly inhibited the proliferation of HL-60 cells and of fibroblast L929 and Swiss 3T3 cells in a dose-dependent manner. The effect of BPB on proliferation is probably through its inhibitory effect on PLA2 activity, since the same doses of BPB which inhibited proliferation also inhibited PLA2 activity determined by [3H]AA release. The importance of PLA2 activity for cell growth was further supported by the effect of two other PLA2 inhibitors, AACOCF3 and scalaradial, which inhibited HL-60 proliferation in a dose-dependent manner. BPB, AACOCF3 and scalaradial significantly increased the doubling time to 32.4 h, 34.0 h and 31.8 h, respectively, compared with 24.6 h in the control. The inhibitory effect of BPB on HL-60 proliferation was reversed by addition of exogenous free AA to HL-60 cells, indicating the importance of this metabolite for the proliferation process. This reversible effect is specific for AA since it was not achieved by other fatty acids like linolenic acid (LA) or oleic acid (OA). Addition of free AA to HL-60 cells did not induce differentiation, as expected. Although BPB, AACOCF3, or scalaradial inhibited proliferation, they did not induce differentiation nor affect the differentiation induced by 1,25(OH)2D3 or RA. These results implicate that PLA2 activity has no regulatory role in differentiation of HL-60 cells. The differential effect of PLA2 inhibitors on proliferation and differentiation of HL-60 cells suggests that these two processes function under different regulatory mechanisms.
Authors:
Y Liu; R Levy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1355     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-11     Completed Date:  1997-04-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  270-80     Citation Subset:  IM    
Affiliation:
Infectious Disease Laboratory, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Acetophenones / pharmacology
Animals
Anti-Inflammatory Agents / pharmacology
Arachidonic Acid / metabolism*,  pharmacology
Arachidonic Acids / pharmacology
Blotting, Northern
Calcitriol / pharmacology
Cell Differentiation*
Cell Division* / drug effects
Enzyme Inhibitors / pharmacology
Granulocytes / cytology*,  drug effects
HL-60 Cells
Homosteroids / pharmacology
Humans
Mice
Phospholipases A / metabolism*
Phospholipases A2
Sesterterpenes
Terpenes / pharmacology
Tetradecanoylphorbol Acetate / pharmacology
Tretinoin / pharmacology
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Anti-Inflammatory Agents; 0/Arachidonic Acids; 0/Enzyme Inhibitors; 0/Homosteroids; 0/Sesterterpenes; 0/Terpenes; 149301-79-1/arachidonyltrifluoromethane; 16561-29-8/Tetradecanoylphorbol Acetate; 302-79-4/Tretinoin; 32222-06-3/Calcitriol; 506-32-1/Arachidonic Acid; 53527-28-9/scalaradial; 99-73-0/4-bromophenacyl bromide; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2

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