Abstract
Osmotic swelling of large unilamellar vesicles (LUVs) causes membrane stretching and thus reduces the lateral packing of lipids. This is demonstrated to modulate strongly the catalytic activity of phospholipase A2 (PLA2) toward a fluorescent phospholipid, 1-palmitoyl-2-[(6-pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) residing in LUVs composed of different unsaturated and saturated phosphatidylcholines. The magnitude of the osmotic pressure gradient delta omega required for maximal PLA2 activity as well as the extent of activation depend on the degree of saturation of the membrane phospholipid acyl chains. More specifically, delta omega needed for maximal hydrolytic activity increases in the sequence DOPC < SOPC < DMPC in accordance with the increment in the intensity of chain-chain van der Waals interactions. Previous studies on the hydrolysis of substrate monolayers by C. adamanteus and N. naja PLA2 revealed maximal hydrolytic rates for these two enzymes to be achieved at lipid packing densities corresponding to surface pressures of 12 and 18 mN m-1, respectively. In keeping with the above the magnitudes of delta omega producing maximal activity of Crotalus adamanteus and Naja naja toward PPDPC/DMPC LUVs were 40 and 20 mOsm/kg, respectively. Our findings suggest a novel possibility of regulating the activity of PLA2 and perhaps also other lipid packing density-dependent enzymes in vivo by osmotic forces applied on cellular membranes. Importantly, our results reveal serendipitously that the responsiveness of membranes to osmotic stress is modulated by the acyl chain composition of the lipids.
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- Arakawa T., Timasheff S. N. Mechanism of poly(ethylene glycol) interaction with proteins. Biochemistry. 1985 Nov 19;24(24):6756–6762. doi: 10.1021/bi00345a005. [DOI] [PubMed] [Google Scholar]
- Arnold K., Zschoernig O., Barthel D., Herold W. Exclusion of poly(ethylene glycol) from liposome surfaces. Biochim Biophys Acta. 1990 Mar;1022(3):303–310. doi: 10.1016/0005-2736(90)90278-v. [DOI] [PubMed] [Google Scholar]
- Baenziger J. E., Jarrell H. C., Smith I. C. Molecular motions and dynamics of a diunsaturated acyl chain in a lipid bilayer: implications for the role of polyunsaturation in biological membranes. Biochemistry. 1992 Apr 7;31(13):3377–3385. doi: 10.1021/bi00128a011. [DOI] [PubMed] [Google Scholar]
- Boguslavsky V., Rebecchi M., Morris A. J., Jhon D. Y., Rhee S. G., McLaughlin S. Effect of monolayer surface pressure on the activities of phosphoinositide-specific phospholipase C-beta 1, -gamma 1, and -delta 1. Biochemistry. 1994 Mar 15;33(10):3032–3037. doi: 10.1021/bi00176a036. [DOI] [PubMed] [Google Scholar]
- Borochov A., Borochov H. Increase in membrane fluidity in liposomes and plant protoplasts upon osmotic swelling. Biochim Biophys Acta. 1979 Feb 2;550(3):546–549. doi: 10.1016/0005-2736(79)90156-1. [DOI] [PubMed] [Google Scholar]
- Brewster J. L., de Valoir T., Dwyer N. D., Winter E., Gustin M. C. An osmosensing signal transduction pathway in yeast. Science. 1993 Mar 19;259(5102):1760–1763. doi: 10.1126/science.7681220. [DOI] [PubMed] [Google Scholar]
- Brophy C. M., Mills I., Rosales O., Isales C., Sumpio B. E. Phospholipase C: a putative mechanotransducer for endothelial cell response to acute hemodynamic changes. Biochem Biophys Res Commun. 1993 Jan 29;190(2):576–581. doi: 10.1006/bbrc.1993.1087. [DOI] [PubMed] [Google Scholar]
- Burack W. R., Biltonen R. L. Lipid bilayer heterogeneities and modulation of phospholipase A2 activity. Chem Phys Lipids. 1994 Sep 6;73(1-2):209–222. doi: 10.1016/0009-3084(94)90182-1. [DOI] [PubMed] [Google Scholar]
- Burack W. R., Yuan Q., Biltonen R. L. Role of lateral phase separation in the modulation of phospholipase A2 activity. Biochemistry. 1993 Jan 19;32(2):583–589. doi: 10.1021/bi00053a025. [DOI] [PubMed] [Google Scholar]
- Burgess S. W., Massenburg D., Yates J., Lentz B. R. Poly(ethylene glycol)-induced lipid mixing but not fusion between synthetic phosphatidylcholine large unilamellar vesicles. Biochemistry. 1991 Apr 30;30(17):4193–4200. doi: 10.1021/bi00231a013. [DOI] [PubMed] [Google Scholar]
- Cordella-Miele E., Miele L., Mukherjee A. B. A novel transglutaminase-mediated post-translational modification of phospholipase A2 dramatically increases its catalytic activity. J Biol Chem. 1990 Oct 5;265(28):17180–17188. [PubMed] [Google Scholar]
- Cornell D. G., Dluhy R. A., Briggs M. S., McKnight C. J., Gierasch L. M. Conformations and orientations of a signal peptide interacting with phospholipid monolayers. Biochemistry. 1989 Apr 4;28(7):2789–2797. doi: 10.1021/bi00433a008. [DOI] [PubMed] [Google Scholar]
- Cunningham B. A., Tsujita T., Brockman H. L. Enzymatic and physical characterization of diacylglycerol-phosphatidylcholine interactions in bilayers and monolayers. Biochemistry. 1989 Jan 10;28(1):32–40. doi: 10.1021/bi00427a006. [DOI] [PubMed] [Google Scholar]
- Deems R. A., Dennis E. A. Characterization and physical properties of the major form of phospholipase A2 from cobra venom (Naja naja naja) that has a molecular weight of 11,000. J Biol Chem. 1975 Dec 10;250(23):9008–9012. [PubMed] [Google Scholar]
- Deems R. A., Eaton B. R., Dennis E. A. Kinetic analysis of phospholipase A2 activity toward mixed micelles and its implications for the study of lipolytic enzymes. J Biol Chem. 1975 Dec 10;250(23):9013–9020. [PubMed] [Google Scholar]
- Dennis E. A., Rhee S. G., Billah M. M., Hannun Y. A. Role of phospholipase in generating lipid second messengers in signal transduction. FASEB J. 1991 Apr;5(7):2068–2077. doi: 10.1096/fasebj.5.7.1901288. [DOI] [PubMed] [Google Scholar]
- Douzou P. Osmotic regulation of gene action. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1657–1661. doi: 10.1073/pnas.91.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eklund K. K., Virtanen J. A., Kinnunen P. K., Kasurinen J., Somerharju P. J. Conformation of phosphatidylcholine in neat and cholesterol-containing liquid-crystalline bilayers. Application of a novel method. Biochemistry. 1992 Sep 15;31(36):8560–8565. doi: 10.1021/bi00151a025. [DOI] [PubMed] [Google Scholar]
- Exton J. H. Signaling through phosphatidylcholine breakdown. J Biol Chem. 1990 Jan 5;265(1):1–4. [PubMed] [Google Scholar]
- Ferguson J. E., Hanley M. R. The role of phospholipases and phospholipid-derived signals in cell activation. Curr Opin Cell Biol. 1991 Apr;3(2):206–212. doi: 10.1016/0955-0674(91)90140-t. [DOI] [PubMed] [Google Scholar]
- Grainger D. W., Reichert A., Ringsdorf H., Salesse C. Hydrolytic action of phospholipase A2 in monolayers in the phase transition region: direct observation of enzyme domain formation using fluorescence microscopy. Biochim Biophys Acta. 1990 Apr 30;1023(3):365–379. doi: 10.1016/0005-2736(90)90128-b. [DOI] [PubMed] [Google Scholar]
- Gruen D. W., Wolfe J. Lateral tensions and pressures in membranes and lipid monolayers. Biochim Biophys Acta. 1982 Jun 14;688(2):572–580. doi: 10.1016/0005-2736(82)90368-6. [DOI] [PubMed] [Google Scholar]
- Haines T. H., Li W., Green M., Cummins H. Z. The elasticity of uniform, unilamellar vesicles of acidic phospholipids during osmotic swelling is dominated by the ionic strength of the media. Biochemistry. 1987 Aug 25;26(17):5439–5447. doi: 10.1021/bi00391a034. [DOI] [PubMed] [Google Scholar]
- Hantz E., Cao A., Escaig J., Taillandier E. The osmotic response of large unilamellar vesicles studied by quasielastic light scattering. Biochim Biophys Acta. 1986 Nov 17;862(2):379–386. doi: 10.1016/0005-2736(86)90241-5. [DOI] [PubMed] [Google Scholar]
- Häussinger D., Lang F. Cell volume in the regulation of hepatic function: a mechanism for metabolic control. Biochim Biophys Acta. 1991 Dec 12;1071(4):331–350. doi: 10.1016/0304-4157(91)90001-d. [DOI] [PubMed] [Google Scholar]
- Izumo S., Nadal-Ginard B., Mahdavi V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci U S A. 1988 Jan;85(2):339–343. doi: 10.1073/pnas.85.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Komuro I., Katoh Y., Kaida T., Shibazaki Y., Kurabayashi M., Hoh E., Takaku F., Yazaki Y. Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J Biol Chem. 1991 Jan 15;266(2):1265–1268. [PubMed] [Google Scholar]
- Kunze H., Nahas N., Traynor J. R., Wurl M. Effects of local anaesthetics on phospholipases. Biochim Biophys Acta. 1976 Jul 20;441(1):93–102. doi: 10.1016/0005-2760(76)90284-8. [DOI] [PubMed] [Google Scholar]
- Lehtonen J. Y., Kinnunen P. K. Changes in the lipid dynamics of liposomal membranes induced by poly(ethylene glycol): free volume alterations revealed by inter- and intramolecular excimer-forming phospholipid analogs. Biophys J. 1994 Jun;66(6):1981–1990. doi: 10.1016/S0006-3495(94)80991-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehtonen J. Y., Kinnunen P. K. Poly(ethylene glycol)-induced and temperature-dependent phase separation in fluid binary phospholipid membranes. Biophys J. 1995 Feb;68(2):525–535. doi: 10.1016/S0006-3495(95)80214-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lichtenberg D., Romero G., Menashe M., Biltonen R. L. Hydrolysis of dipalmitoylphosphatidylcholine large unilamellar vesicles by porcine pancreatic phospholipase A2. J Biol Chem. 1986 Apr 25;261(12):5334–5340. [PubMed] [Google Scholar]
- MacDonald R. C., MacDonald R. I., Menco B. P., Takeshita K., Subbarao N. K., Hu L. R. Small-volume extrusion apparatus for preparation of large, unilamellar vesicles. Biochim Biophys Acta. 1991 Jan 30;1061(2):297–303. doi: 10.1016/0005-2736(91)90295-j. [DOI] [PubMed] [Google Scholar]
- Maloney K. M., Grainger D. W. Phase separated anionic domains in ternary mixed lipid monolayers at the air-water interface. Chem Phys Lipids. 1993 Apr;65(1):31–42. doi: 10.1016/0009-3084(93)90079-i. [DOI] [PubMed] [Google Scholar]
- Martinac B., Adler J., Kung C. Mechanosensitive ion channels of E. coli activated by amphipaths. Nature. 1990 Nov 15;348(6298):261–263. doi: 10.1038/348261a0. [DOI] [PubMed] [Google Scholar]
- Martinac B., Buechner M., Delcour A. H., Adler J., Kung C. Pressure-sensitive ion channel in Escherichia coli. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2297–2301. doi: 10.1073/pnas.84.8.2297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mathai J. C., Sauna Z. E., John O., Sitaramam V. Rate-limiting step in electron transport. Osmotically sensitive diffusion of quinones through voids in the bilayer. J Biol Chem. 1993 Jul 25;268(21):15442–15454. [PubMed] [Google Scholar]
- Mayer R. J., Marshall L. A. New insights on mammalian phospholipase A2(s); comparison of arachidonoyl-selective and -nonselective enzymes. FASEB J. 1993 Feb 1;7(2):339–348. doi: 10.1096/fasebj.7.2.8440410. [DOI] [PubMed] [Google Scholar]
- Momsen W. E., Brockman H. L. Effects of colipase and taurodeoxycholate on the catalytic and physical properties of pancreatic lipase B at an oil water interface. J Biol Chem. 1976 Jan 25;251(2):378–383. [PubMed] [Google Scholar]
- Morris C. E. Mechanosensitive ion channels. J Membr Biol. 1990 Feb;113(2):93–107. doi: 10.1007/BF01872883. [DOI] [PubMed] [Google Scholar]
- Morris C. E., Sigurdson W. J. Stretch-inactivated ion channels coexist with stretch-activated ion channels. Science. 1989 Feb 10;243(4892):807–809. doi: 10.1126/science.2536958. [DOI] [PubMed] [Google Scholar]
- Mui B. L., Cullis P. R., Evans E. A., Madden T. D. Osmotic properties of large unilamellar vesicles prepared by extrusion. Biophys J. 1993 Feb;64(2):443–453. doi: 10.1016/S0006-3495(93)81385-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mui B. L., Cullis P. R., Pritchard P. H., Madden T. D. Influence of plasma on the osmotic sensitivity of large unilamellar vesicles prepared by extrusion. J Biol Chem. 1994 Mar 11;269(10):7364–7370. [PubMed] [Google Scholar]
- Mustonen P., Kinnunen P. K. Activation of phospholipase A2 by adriamycin in vitro. Role of drug-lipid interactions. J Biol Chem. 1991 Apr 5;266(10):6302–6307. [PubMed] [Google Scholar]
- Mustonen P., Lehtonen J., Kõiv A., Kinnunen P. K. Effects of sphingosine on peripheral membrane interactions: comparison of adriamycin, cytochrome c, and phospholipase A2. Biochemistry. 1993 May 25;32(20):5373–5380. doi: 10.1021/bi00071a012. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992 Oct 23;258(5082):607–614. doi: 10.1126/science.1411571. [DOI] [PubMed] [Google Scholar]
- Oliet S. H., Bourque C. W. Mechanosensitive channels transduce osmosensitivity in supraoptic neurons. Nature. 1993 Jul 22;364(6435):341–343. doi: 10.1038/364341a0. [DOI] [PubMed] [Google Scholar]
- Op den Kamp J. A., Kauerz M. T., van Deenen L. L. Action of pancreatic phospholipase A2 on phosphatidylcholine bilayers in different physical states. Biochim Biophys Acta. 1975 Oct 6;406(2):169–177. doi: 10.1016/0005-2736(75)90001-2. [DOI] [PubMed] [Google Scholar]
- Pattus F., Slotboom A. J., de Haas G. H. Regulation of phospholipase A2 activity by the lipid-water interface: a monolayer approach. Biochemistry. 1979 Jun 26;18(13):2691–2697. doi: 10.1021/bi00580a001. [DOI] [PubMed] [Google Scholar]
- Pieroni G., Verger R. Hydrolysis of mixed monomolecular films of triglyceride/lecithin by pancreatic lipase. J Biol Chem. 1979 Oct 25;254(20):10090–10094. [PubMed] [Google Scholar]
- Poulin R., Pegg A. E. Regulation of ornithine decarboxylase expression by anisosmotic shock in alpha-difluoromethylornithine-resistant L1210 cells. J Biol Chem. 1990 Mar 5;265(7):4025–4032. [PubMed] [Google Scholar]
- Radvanyi F., Jordan L., Russo-Marie F., Bon C. A sensitive and continuous fluorometric assay for phospholipase A2 using pyrene-labeled phospholipids in the presence of serum albumin. Anal Biochem. 1989 Feb 15;177(1):103–109. doi: 10.1016/0003-2697(89)90022-5. [DOI] [PubMed] [Google Scholar]
- Rao N. M., Sundaram C. S. Sensitivity of phospholipase C (Bacillus cereus) activity to lipid packing in sonicated lipid mixtures. Biochemistry. 1993 Aug 24;32(33):8547–8552. doi: 10.1021/bi00084a022. [DOI] [PubMed] [Google Scholar]
- Rogalska E., Ransac S., Verger R. Controlling lipase stereoselectivity via the surface pressure. J Biol Chem. 1993 Jan 15;268(2):792–794. [PubMed] [Google Scholar]
- Rutkowski C. A., Williams L. M., Haines T. H., Cummins H. Z. The elasticity of synthetic phospholipid vesicles obtained by photon correlation spectroscopy. Biochemistry. 1991 Jun 11;30(23):5688–5696. doi: 10.1021/bi00237a008. [DOI] [PubMed] [Google Scholar]
- Sadoshima J., Izumo S. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. EMBO J. 1993 Apr;12(4):1681–1692. doi: 10.1002/j.1460-2075.1993.tb05813.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sen A., Isac T. V., Hui S. W. Bilayer packing stress and defects in mixed dilinoleoylphosphatidylethanolamine and palmitoyloleoylphosphatidylcholine and their susceptibility to phospholipase A2. Biochemistry. 1991 May 7;30(18):4516–4521. doi: 10.1021/bi00232a021. [DOI] [PubMed] [Google Scholar]
- Shinomura T., Asaoka Y., Oka M., Yoshida K., Nishizuka Y. Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5149–5153. doi: 10.1073/pnas.88.12.5149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Souvignet C., Pelosin J. M., Daniel S., Chambaz E. M., Ransac S., Verger R. Activation of protein kinase C in lipid monolayers. J Biol Chem. 1991 Jan 5;266(1):40–44. [PubMed] [Google Scholar]
- Tang D., Chong P. L. E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations. Biophys J. 1992 Oct;63(4):903–910. doi: 10.1016/S0006-3495(92)81672-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thuren T., Tulkki A. P., Virtanen J. A., Kinnunen P. K. Triggering of the activity of phospholipase A2 by an electric field. Biochemistry. 1987 Aug 11;26(16):4907–4910. doi: 10.1021/bi00390a002. [DOI] [PubMed] [Google Scholar]
- Thuren T., Virtanen J. A., Kinnunen P. K. Control of the action of phospholipases A by "vertical compression" of the substrate monolayer. Biochemistry. 1987 Sep 8;26(18):5816–5819. doi: 10.1021/bi00392a035. [DOI] [PubMed] [Google Scholar]
- Thuren T., Virtanen J. A., Verger R., Kinnunen P. K. Hydrolysis of 1-palmitoyl-2-[6-(pyren-1-yl)]hexanoyl-sn-glycero- 3-phospholipids by phospholipase A2: effect of the polar head-group. Biochim Biophys Acta. 1987 Feb 23;917(3):411–417. doi: 10.1016/0005-2760(87)90120-2. [DOI] [PubMed] [Google Scholar]
- Tilcock C. P., Fisher D. The interaction of phospholipid membranes with poly(ethylene glycol). Vesicle aggregation and lipid exchange. Biochim Biophys Acta. 1982 Jun 14;688(2):645–652. doi: 10.1016/0005-2736(82)90375-3. [DOI] [PubMed] [Google Scholar]
- Tilly B. C., van den Berghe N., Tertoolen L. G., Edixhoven M. J., de Jonge H. R. Protein tyrosine phosphorylation is involved in osmoregulation of ionic conductances. J Biol Chem. 1993 Sep 25;268(27):19919–19922. [PubMed] [Google Scholar]
- Tsujita T., Muderhwa J. M., Brockman H. L. Lipid-lipid interactions as regulators of carboxylester lipase activity. J Biol Chem. 1989 May 25;264(15):8612–8618. [PubMed] [Google Scholar]
- Vainio P., Virtanen J. A., Kinnunen P. K., Gotto A. M., Jr, Sparrow J. T., Pattus F., Bougis P., Verger R. Action of lipoprotein lipase on mixed triacylglycerol/phosphatidylcholine monolayers. Activation by apolipoprotein C-II. J Biol Chem. 1983 May 10;258(9):5477–5482. [PubMed] [Google Scholar]
- Venable M. E., Blobe G. C., Obeid L. M. Identification of a defect in the phospholipase D/diacylglycerol pathway in cellular senescence. J Biol Chem. 1994 Oct 21;269(42):26040–26044. [PubMed] [Google Scholar]
- Verger R., Mieras M. C., de Haas G. H. Action of phospholipase A at interfaces. J Biol Chem. 1973 Jun 10;248(11):4023–4034. [PubMed] [Google Scholar]
- Verheij H. M., Boffa M. C., Rothen C., Bryckaert M. C., Verger R., de Haas G. H. Correlation of enzymatic activity and anticoagulant properties of phospholipase A2. Eur J Biochem. 1980 Nov;112(1):25–32. doi: 10.1111/j.1432-1033.1980.tb04982.x. [DOI] [PubMed] [Google Scholar]
- Wang N., Butler J. P., Ingber D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993 May 21;260(5111):1124–1127. doi: 10.1126/science.7684161. [DOI] [PubMed] [Google Scholar]
- Watson P. A. Function follows form: generation of intracellular signals by cell deformation. FASEB J. 1991 Apr;5(7):2013–2019. doi: 10.1096/fasebj.5.7.1707019. [DOI] [PubMed] [Google Scholar]
- Wery J. P., Schevitz R. W., Clawson D. K., Bobbitt J. L., Dow E. R., Gamboa G., Goodson T., Jr, Hermann R. B., Kramer R. M., McClure D. B. Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2 A resolution. Nature. 1991 Jul 4;352(6330):79–82. doi: 10.1038/352079a0. [DOI] [PubMed] [Google Scholar]
- Yamazaki M., Ohnishi S., Ito T. Osmoelastic coupling in biological structures: decrease in membrane fluidity and osmophobic association of phospholipid vesicles in response to osmotic stress. Biochemistry. 1989 May 2;28(9):3710–3715. doi: 10.1021/bi00435a013. [DOI] [PubMed] [Google Scholar]
- van den Berg J. J., Op den Kamp J. A., Lubin B. H., Kuypers F. A. Conformational changes in oxidized phospholipids and their preferential hydrolysis by phospholipase A2: a monolayer study. Biochemistry. 1993 May 11;32(18):4962–4967. doi: 10.1021/bi00069a035. [DOI] [PubMed] [Google Scholar]