scholarly journals Enhanced hydrolysis of phosphatidylcholine by human group II non-pancreatic secreted phospholipase A2 as a result of interfacial activation by specific anions. Potential role of cholesterol sulphate

1995 ◽  
Vol 308 (2) ◽  
pp. 507-512 ◽  
Author(s):  
A R Kinkaid ◽  
D C Wilton
Keyword(s):  
Phospholipase A2 ◽  
Anionic Phospholipid ◽  
Interfacial Activation ◽  
Secreted Phospholipase A2 ◽  
Cell Plasma ◽  
Membrane Hydrolysis ◽  
Membrane Bound ◽  
Group Ii ◽  
Hydrolysis Of

The extracellular concentration of the Group II human non-pancreatic secreted phospholipase A2 (hnpsPLA2) is elevated in a variety of inflammatory disorders. This enzyme is remarkable because it demonstrates almost zero activity with egg phosphatidylcholine (PC) or synthetic dioleoyl-phosphatidylcholine (DOPC) as substrate, but expresses high activity with the anionic phospholipid dioleoyl-phosphatidylglycerol (DOPG), a feature shared with the Group II enzyme from rat liver. The presence of certain membrane-bound anions can enhance hydrolysis of PC by the mammalian secreted PLA2S. In this study the ability of various non-polar anions to stimulate DOPC hydrolysis by secreted PLA2S has been investigated. The naturally occurring membrane anion, cholesterol sulphate, was particularly effective in stimulating the hydrolysis of both DOPC and also 1-stearoyl-2-arachidonyl phosphatidylcholine by hnpsPLA2. Activation of DOPC hydrolysis was also achieved with dioleoyl-phosphatidylserine (DOPS); however, DOPS was less effective than cholesterol sulphate. In contrast, the dianion dioleoyl-phosphatidic acid, a known activator of pig pancreatic PLA2, failed to activate the human enzyme. It remains to be established whether cell plasma-membrane hydrolysis by extracellular hnpsPLA2 can be activated in vivo by the presence of suitable membrane anions such as cholesterol sulphate and thus promote an inflammatory response within the cell.

scholarly journals Inhibition of human cytosolic phospholipase A2 by human annexin V

1998 ◽  
Vol 329 (2) ◽  
pp. 369-372 ◽  
Author(s):  
G. Andrew BUCKLAND ◽  
C. David WILTON
Keyword(s):  
Phospholipase A2 ◽  
Annexin V ◽  
High Molecular Mass ◽  
Anionic Phospholipid ◽  
Annexin 1 ◽  
Cytosolic Phospholipase ◽  
Cytosolic Pla2 ◽  
Hydrolysis Of

The ability of annexins, particularly annexin 1 (lipocortin 1), to inhibit phospholipase A2 (PLA2) is well known and a substrate depletion mechanism is now widely accepted as the explanation for most inhibitory studies. However, there are only a very limited number of reported studies involving annexins and the high-molecular-mass cytosolic PLA2 (cPLA2). In this study we have examined the effect of human recombinant annexin V, a potentially abundant cytosolic protein, on the ability of human recombinant cPLA2 to hydrolyse a variety of phospholipid substrates. The results show clearly that, under the conditions of our study, annexin V can inhibit cPLA2 activity by a mechanism of substrate depletion and that this inhibition is dependent on the nature of the phospholipids and the concentration of Ca2+ ions in the assay. The hydrolysis of 1-stearoyl 2-arachidonyl phosphatidylcholine by cPLA2 was not significantly affected by annexin V over a range of Ca2+ concentrations (1 μM-2.5 mM), a result that presumably reflects the zwitterionic nature of the phospholipid and the known inability of annexins to bind to such interfaces. In contrast, the hydrolysis of dioleoyl phosphatidylglycerol, which is an effective anionic phospholipid substrate for this enzyme, and more significantly that of 1-stearoyl 2-arachidonyl phosphatidic acid, were readily inhibited by annexin V, although these effects were Ca2+-dependent. The Ca2+ concentrations required for inhibition in the assay system in vitro are greater than those associated with Ca2+-stimulated events within the cell, suggesting that a role for annexin V in regulating cPLA2 activity might not involve a substrate depletion mechanism in vivo unless factors in addition to Ca2+ and phospholipids contribute to the binding of annexin V to cell membranes.

scholarly journals Group V Secreted Phospholipase A2 Is Upregulated by IL-4 in Human Macrophages and Mediates Phagocytosis via Hydrolysis of Ethanolamine Phospholipids

2015 ◽  
Vol 194 (7) ◽  
pp. 3327-3339 ◽  
Author(s):  
Julio M. Rubio ◽  
Juan P. Rodríguez ◽  
Luis Gil-de-Gómez ◽  
Carlos Guijas ◽  
María A. Balboa ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Group V ◽  
Human Macrophages ◽  
Secreted Phospholipase A2 ◽  
Hydrolysis Of

Kinetic Basis for the Substrate Specificity during Hydrolysis of Phospholipids by Secreted Phospholipase A2†

Biochemistry ◽  
1996 ◽  
Vol 35 (29) ◽  
pp. 9375-9384 ◽  
Author(s):  
Joseph Rogers ◽  
Bao-Zhu Yu ◽  
Spyros V. Serves ◽  
Gerasimos M. Tsivgoulis ◽  
Demetrios N. Sotiropoulos ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Phospholipase A2 ◽  
Secreted Phospholipase A2 ◽  
Hydrolysis Of

scholarly journals New Insights into the Interfacial Activation of Secreted Phospholipase A2

2010 ◽  
Vol 98 (3) ◽  
pp. 648a
Author(s):  
Jeffrey L. Urbauer ◽  
Kathleen N. Nemec ◽  
Suren A. Tatulian
Keyword(s):  
Phospholipase A2 ◽  
Interfacial Activation ◽  
Secreted Phospholipase A2

scholarly journals cPLA2α and EHD1 interact and regulate the vesiculation of cholesterol-rich, GPI-anchored, protein-containing endosomes

2012 ◽  
Vol 23 (10) ◽  
pp. 1874-1888 ◽  
Author(s):  
Bishuang Cai ◽  
Steve Caplan ◽  
Naava Naslavsky
Keyword(s):  
Phospholipase A2 ◽  
Membrane Curvature ◽  
Cytosolic Phospholipase ◽  
Early Endosomes ◽  
Lysophospholipid Acyltransferase ◽  
Curved Membranes ◽  
Hydrolysis Of

The lipid modifier phospholipase A2 catalyzes the hydrolysis of phospholipids to inverted-cone–shaped lysophospholipids that contribute to membrane curvature and/or tubulation. Conflicting findings exist regarding the function of cytosolic phospholipase A2 (cPLA2) and its role in membrane regulation at the Golgi and early endosomes. However, no studies addressed the role of cPLA2 in the regulation of cholesterol-rich membranes that contain glycosylphosphatidylinositol-anchored proteins (GPI-APs). Our studies support a role for cPLA2α in the vesiculation of GPI-AP–containing membranes, using endogenous CD59 as a model for GPI-APs. On cPLA2α depletion, CD59-containing endosomes became hypertubular. Moreover, accumulation of lysophospholipids induced by a lysophospholipid acyltransferase inhibitor extensively vesiculated CD59-containing endosomes. However, overexpression of cPLA2α did not increase the endosomal vesiculation, implying a requirement for additional factors. Indeed, depletion of the “pinchase” EHD1, a C-terminal Eps15 homology domain (EHD) ATPase, also induced hypertubulation of CD59-containing endosomes. Furthermore, EHD1 and cPLA2α demonstrated in situ proximity (<40 nm) and interacted in vivo. The results presented here provide evidence that the lipid modifier cPLA2α and EHD1 are involved in the vesiculation of CD59-containing endosomes. We speculate that cPLA2α induces membrane curvature and allows EHD1, possibly in the context of a complex, to sever the curved membranes into vesicles.

scholarly journals The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia

2015 ◽  
Vol 212 (11) ◽  
pp. 1901-1919 ◽  
Author(s):  
Kei Yamamoto ◽  
Yoshimi Miki ◽  
Mariko Sato ◽  
Yoshitaka Taketomi ◽  
Yasumasa Nishito ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Bioactive Lipids ◽  
Epidermal Lipids ◽  
Secreted Phospholipase A2 ◽  
Lipid Species ◽  
Ethanolamine Plasmalogen ◽  
Epidermal Homeostasis ◽  
Novel Drug

Epidermal lipids are important for skin homeostasis. However, the entire picture of the roles of lipids, particularly nonceramide lipid species, in epidermal biology still remains obscure. Here, we report that PLA2G2F, a functionally orphan-secreted phospholipase A2 expressed in the suprabasal epidermis, regulates skin homeostasis and hyperplasic disorders. Pla2g2f−/− mice had a fragile stratum corneum and were strikingly protected from psoriasis, contact dermatitis, and skin cancer. Conversely, Pla2g2f-overexpressing transgenic mice displayed psoriasis-like epidermal hyperplasia. Primary keratinocytes from Pla2g2f−/− mice showed defective differentiation and activation. PLA2G2F was induced by calcium or IL-22 in keratinocytes and preferentially hydrolyzed ethanolamine plasmalogen-bearing docosahexaenoic acid secreted from keratinocytes to give rise to unique bioactive lipids (i.e., protectin D1 and 9S-hydroxyoctadecadienoic acid) that were distinct from canonical arachidonate metabolites (prostaglandins and leukotrienes). Ethanolamine lysoplasmalogen, a PLA2G2F-derived marker product, rescued defective activation of Pla2g2f−/− keratinocytes both in vitro and in vivo. Our results highlight PLA2G2F as a previously unrecognized regulator of skin pathophysiology and point to this enzyme as a novel drug target for epidermal-hyperplasic diseases.

Sign in / Sign up

Export Citation Format

Share Document