PMID- 8142396
OWN - NLM
STAT- MEDLINE
DCOM- 19940505
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 33
IP  - 13
DP  - 1994 Apr 5
TI  - Effects of phorbol myristate acetate on the synthesis of 
      5-oxo-6,8,11,14-eicosatetraenoic acid by human polymorphonuclear leukocytes.
PG  - 3927-33
AB  - 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a newly discovered 
      chemotactic agent for human polymorphonuclear leukocytes (PMNL) which has potent 
      stimulatory effects on cytosolic calcium levels in these cells. Although we have 
      shown that it is synthesized from 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid 
      (5-HETE) by a highly specific microsomal dehydrogenase, little is known about the 
      synthesis of this substance by intact PMNL. In the present study we found that in 
      contrast to PMNL microsomes, intact, unstimulated PMNL produced relatively small 
      amounts of 5-oxo-ETE from 5-HETE, but instead converted 5-HETE primarily to its 
      omega-oxidation product, 5,20-diHETE. However, preincubation of PMNL with phorbol 
      myristate acetate (PMA; EC50, ca. 4 nM) dramatically increased the ratio of 
      5-oxo-ETE to 5,20-diHETE from 0.07 in its absence to 1.85 in the presence of 100 
      nM PMA. Both effects were completely reversed by staurosporine, indicated that 
      they were mediated by a protein kinase. PMA also stimulated the formation of 
      5-oxo-ETE, 5-HETE, and leukotriene B4 (LTB4) from exogenous arachidonic acid. The 
      greatest enhancement was observed for 5-oxo-ETE, which, under all conditions, was 
      produced in greater quantities than LTB4. PMA stimulated the formation of 
      5-oxo-ETE by PMNL stimulated with either A23187 or zymosan. A23187-stimulated 
      PMNL initially produced more LTB4 than 5-oxo-ETE, but at longer time points, 
      5-oxo-ETE predominated. These results demonstrate that PMA-activated human PMNL 
      can synthesize substantial amounts of 5-oxo-ETE and raise the possibility that 
      this substance may be an important inflammatory mediator.
FAU - Powell, W S
AU  - Powell WS
AD  - Meakins-Christie Laboratories, Department of Medicine, McGill University, 
      Montreal, Quebec, Canada.
FAU - Zhang, Y
AU  - Zhang Y
FAU - Gravel, S
AU  - Gravel S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Arachidonic Acids)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 107373-23-9 (5,20-dihydroxy-6,8,11,14-eicosatetraenoic acid)
RN  - 126432-17-5 (5-oxo-6,8,11,14-eicosatetraenoic acid)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 467RNW8T91 (5-hydroxy-6,8,11,14-eicosatetraenoic acid)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Arachidonic Acid/metabolism
MH  - Arachidonic Acids/*biosynthesis
MH  - Chemotactic Factors/biosynthesis
MH  - Chemotaxis, Leukocyte
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/metabolism
MH  - Neutrophils/drug effects/*metabolism
MH  - Protein Kinase C/physiology
MH  - Tetradecanoylphorbol Acetate/*pharmacology
EDAT- 1994/04/05 00:00
MHDA- 1994/04/05 00:01
CRDT- 1994/04/05 00:00
PHST- 1994/04/05 00:00 [pubmed]
PHST- 1994/04/05 00:01 [medline]
PHST- 1994/04/05 00:00 [entrez]
AID - 10.1021/bi00179a019 [doi]
PST - ppublish
SO  - Biochemistry. 1994 Apr 5;33(13):3927-33. doi: 10.1021/bi00179a019.