+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Contribution of Type II PLA2 to prostaglandin formation: A study using a Type II PLA2 specific inhibitor SB 203347

Contribution of Type II PLA2 to prostaglandin formation: A study using a Type II PLA2 specific inhibitor SB 203347

Prostaglandins & Other Lipid Mediators 57(5-6): 361-370

Arachidonic acid (AA) mobilization by phospholipase A2 (PLA2) and subsequent prostaglandin synthesis is considered to be a pivotal event in inflammation. The purpose of this study was to assess the efficacy of a Type II PLA2 specific inhibitor, SB 203347, in reducing prostaglandin production in Type II PLA2-transfected Chinese hamster ovary (CHO) cells and in human placenta. In both experimental models utilised, Type II PLA2 represents the principal isozyme contributing to total PLA2 enzymatic activity. PLA2 enzymatic activity released into cell culture media and placental explant media was quantified by radiolabelled substrate assay [14C-phosphatidylethanolamine (PE)]. Immunoreactive prostaglandin F2alpha (PGF2alpha) concentrations were determined by radioimmunoassay. SB 203347 (at 0.1-10 microM final concentration) inhibited PLA2 enzymatic activity released by Zn++ -activated CHO cells by up to 60% (P<0.0001). The concentration of PGF2alpha present in culture media was concomitantly reduced by up to 90% (P<0.0001). Similar results were observed for human placental explants. Treatment of human placental explants with SB 203347 (1 microM final concentration) significantly reduced PLA2 enzymatic activity recovered in media after 24 h incubation (P<0.0001; n = 10). Incubation media PGF2alpha concentrations were also reduced by 60% (P<0.00001). The addition of endogenous arachidonic acid (30 microM final concentration) significantly attenuated SB 203347-inhibition of PGF2alpha release (P<0.01). The data obtained in this study are consistent with the hypothesis that Type II PLA2 contributes to the liberation of arachidonic acid for prostanoid formation in human placenta and in cells that abundantly express this isozyme.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 010382145

Download citation: RISBibTeXText

PMID: 10480490

DOI: 10.1016/s0090-6980(99)00012-x

Related references

Type IIA secretory PLA2-mediated delayed PGE2 biosynthesis is regulated by the products of the cytosolic PLA2. Advances in Experimental Medicine and Biology 507: 9, 2002

Secretory type II PLA2 immunoreactivity and PLA2 enzymatic activity in human gestational tissues before, during and after spontaneous-onset labour at term. Placenta 20(1): 21-26, 1999

PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor. Febs Letters 578(3): 269-274, 2004

SB-203347, a 14-kilodalton, PLA2 inhibitor, reduces ear edema, neutrophil influx, and epidermal proliferation in a murine phorbol 12- myristate 13-acetate-induced ear inflammation model. Journal of Investigative Dermatology 117(2): 439, 2001

Studies on the measurement of phospholipase A2 (PLA2) and PLA2 inhibitor activities in ram semen. Animal Reproduction Science 56(2): 107-121, 1999

Productive presentation of bee venom phospholipase a2 pla2 by tetanus toxoid tt specific b cells to pla2 specific t cells results in the production of anti tt antibodies. Journal of Cellular Biochemistry Suppl. (12 Part B): 127, 1988

Genetic invalidation of Lp-PLA 2 as a therapeutic target: Large-scale study of five functional Lp-PLA 2 -lowering alleles. European Journal of Preventive Cardiology 24(5): 492-504, 2017

Development of a monoclonal antibody capable of differentiating platelet PLA1/PLA1, PLA1/PLA2 and PLA2/PLA2 genotypes. British Journal of Haematology 81(1): 113-117, 1992

Isolation of a snake venom phospholipase A2 (PLA2) inhibitor (AIPLAI) from leaves of Azadirachta indica (Neem): mechanism of PLA2 inhibition by AIPLAI in vitro condition. Toxicon 51(8): 1548-1553, 2008

Phox activity of differentiated PLB-985 cells is enhanced, in an agonist specific manner, by the PLA2 activity of Prdx6-PLA2. European Journal of Immunology 42(6): 1609-1617, 2012

Platelet glycoprotein IIb/IIIa PlA2/PlA2 homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men: The Copenhagen City Heart Study. Journal of the American College of Cardiology 42(4): 661-667, 2003

Structure-activity relationships leading to WAY-121,520, a tris aryl-type, indomethacin-based, phospholipase A2(PLA2)/leukotriene biosynthesis inhibitor. Inflammation Research 39(1 Suppl.): C33-C35, 1993

Structure-activity relationships leading to WAY-121,520, a tris aryl-type, indomethacin-based, phospholipase A2 (PLA2)/leukotriene biosynthesis inhibitor. Agents and Actions 39 Spec No: C33-C35, 1993

Apical ANG II-stimulated PLA2 activity and Na+ flux: a potential role for Ca2+-independent PLA2. American Journal of Physiology 273(4): F554-F562, 1997

Inhibition of endosome fusion by phospholipase A2 (PLA2) inhibitors points to a role for PLA2 in endocytosis. Proceedings of the National Academy of Sciences of the United States of America 90(21): 10255-9, 1993