Inhibition of macrophage Ca(2+)-independent phospholipase A2 by bromoenol lactone and trifluoromethyl ketones - PubMed (original) (raw)
. 1995 Jan 6;270(1):445-50.
doi: 10.1074/jbc.270.1.445.
Affiliations
- PMID: 7814408
- DOI: 10.1074/jbc.270.1.445
Free article
Inhibition of macrophage Ca(2+)-independent phospholipase A2 by bromoenol lactone and trifluoromethyl ketones
E J Ackermann et al. J Biol Chem. 1995.
Free article
Abstract
A novel Ca(2+)-independent phospholipase A2 (PLA2) has recently been purified from the murine macrophage-like cell line P388D1 (Ackermann, E. J., Kempner, E. S., and Dennis, E. A. (1994) J. Biol. Chem. 269, 9227-9233). This enzyme is now shown to be inhibited by palmitoyl trifluoromethyl ketone (PACOCF3), arachidonyl trifluoromethyl ketone (AACOCF3), and a bromoenol lactone (BEL). Both PACOCF3 and AACOCF3 were found to inhibit the macrophage PLA2 in a concentration-dependent manner. PACOCF3 was found to be approximately 4-fold more potent than AACOCF3, with IC50 values of 3.8 microM (0.0075 mol fraction) and 15 microM (0.028 mol fraction), respectively. Reaction progress curves in the presence of either inhibitor were found to be linear, and the PACOCF3.PLA2 complex rapidly dissociated upon dilution. BEL was also found to inhibit the macrophage PLA2 in a concentration-dependent manner, with half-maximal inhibition observed at 60 nM after a 5-min preincubation at 40 degrees C. Inhibition was not reversed after extensive dilution of the enzyme into assay buffer. Treatment of the PLA2 with BEL resulted in a linear, time-dependent inactivation of activity, and the rate of this inactivation was diminished in the presence of PACOCF3. In addition, PLA2 treated with [3H]BEL resulted in the covalent labeling of a major band at M(r) 80,000. Inactivation of the PLA2 by 5,5'-dithiobis(2-nitrobenzoic acid) prior to treatment with [3H]BEL resulted in the near complete lack of labeling consistent with covalent irreversible suicide inhibition of the enzyme. The labeling of a M(r) 80,000 band rather than a M(r) 40,000 band upon treatment with [3H]BEL distinguishes the macrophage Ca(2+)-independent PLA2 from a previously identified myocardial Ca(2+)-independent PLA2 and provides strong evidence that the M(r) 80,000 protein is the catalytic subunit.
Similar articles
- Identity between the Ca2+-independent phospholipase A2 enzymes from P388D1 macrophages and Chinese hamster ovary cells.
Balboa MA, Balsinde J, Jones SS, Dennis EA. Balboa MA, et al. J Biol Chem. 1997 Mar 28;272(13):8576-80. doi: 10.1074/jbc.272.13.8576. J Biol Chem. 1997. PMID: 9079688 - Bromoenol lactone inhibits magnesium-dependent phosphatidate phosphohydrolase and blocks triacylglycerol biosynthesis in mouse P388D1 macrophages.
Balsinde J, Dennis EA. Balsinde J, et al. J Biol Chem. 1996 Dec 13;271(50):31937-41. doi: 10.1074/jbc.271.50.31937. J Biol Chem. 1996. PMID: 8943239 - Glyburide-reversible cardioprotective effects of calcium-independent phospholipase A2 inhibition in ischemic rat hearts.
Sargent CA, Wilde MW, Dzwonczyk S, Tuttle JG, Murray HN, Atwal K, Grover GJ. Sargent CA, et al. Cardiovasc Res. 1996 Feb;31(2):270-7. Cardiovasc Res. 1996. PMID: 8730404 - Ca2+-independent phospholipase A2 inhibitor impairs spatial memory of mice.
Fujita S, Ikegaya Y, Nishiyama N, Matsuki N. Fujita S, et al. Jpn J Pharmacol. 2000 Jul;83(3):277-8. doi: 10.1254/jjp.83.277. Jpn J Pharmacol. 2000. PMID: 10952080
Cited by
- Cardiolipin remodeling maintains the inner mitochondrial membrane in cells with saturated lipidomes.
Venkatraman K, Budin I. Venkatraman K, et al. J Lipid Res. 2024 Aug;65(8):100601. doi: 10.1016/j.jlr.2024.100601. Epub 2024 Jul 20. J Lipid Res. 2024. PMID: 39038656 Free PMC article. - Four phospholipase A2 genes encoded in the western flower thrips genome and their functional differentiation in mediating development and immunity.
Esmaeily M, Kim Y. Esmaeily M, et al. Sci Rep. 2024 Apr 29;14(1):9766. doi: 10.1038/s41598-024-60522-8. Sci Rep. 2024. PMID: 38684777 Free PMC article. - Tlr4 Deletion Modulates Cytokine and Extracellular Matrix Expression in Chronic Spinal Cord Injury, Leading to Improved Secondary Damage and Functional Recovery.
Ryan F, Francos-Quijorna I, Hernández-Mir G, Aquino C, Schlapbach R, Bradbury EJ, David S. Ryan F, et al. J Neurosci. 2024 Feb 7;44(6):e0778232023. doi: 10.1523/JNEUROSCI.0778-23.2023. J Neurosci. 2024. PMID: 38326029 Free PMC article. - Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase A2.
Mangini M, D'Angelo R, Vinciguerra C, Payré C, Lambeau G, Balestrieri B, Charles JF, Mariggiò S. Mangini M, et al. Front Cell Dev Biol. 2022 Aug 29;10:966950. doi: 10.3389/fcell.2022.966950. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36105351 Free PMC article. - Functions and mechanisms of cytosolic phospholipase A2 in central nervous system trauma.
Zhang HJ, Chen YT, Hu XL, Cai WT, Wang XY, Ni WF, Zhou KL. Zhang HJ, et al. Neural Regen Res. 2023 Feb;18(2):258-266. doi: 10.4103/1673-5374.346460. Neural Regen Res. 2023. PMID: 35900400 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous