scholarly journals Effects of glycosaminoglycans and glycosphingolipids on cytosolic phospholipases A2 from bovine brain

1994 ◽  
Vol 299 (1) ◽  
pp. 91-95 ◽  
Author(s):  
H C Yang ◽  
A A Farooqui ◽  
L A Horrocks
Keyword(s):  
Phospholipase A2 ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Bovine Brain ◽  
Heat Inactivation ◽  
Dependent Manner ◽  
Membrane Function ◽  
Phospholipases A2 ◽  
Ethanolamine Plasmalogen ◽  
Cytosolic Phospholipases A2

Two forms of Ca(2+)-independent cytosolic phospholipase A2 activity (110 kDa and 39 kDa) were found in bovine brain. They were separated by Sephadex G-75 column chromatography. The 110 kDa phospholipase A2 was much more active with phosphatidylethanolamine and was not affected by glycosaminoglycans, whereas the 39 kDa phospholipase A2 was much more active with ethanolamine plasmalogen and was markedly inhibited by glycosaminoglycans. Heparan sulphate was the most potent inhibitor, followed by chondroitin sulphate, hyaluronic acid and heparin. Gangliosides, especially the GM3 ganglioside, but not other glycosphingolipids, inhibited the activity of the 39 kDa phospholipase A2 in a dose-dependent manner. The heat-inactivation profiles of the 110 kDa and 39 kDa phospholipases A2 provide further evidence for the differences between these cytosolic enzymes. Interactions between glycosaminoglycans, gangliosides and phospholipases A2 may be involved in the maintenance of membrane function.

Annexins: Novel Ca2+-Dependent Regulators of Membrane Function

Physiology ◽  
1995 ◽  
Vol 10 (4) ◽  
pp. 171-176
Author(s):  
MA Kaetzel ◽  
JR Dedman
Keyword(s):  
Phospholipase A2 ◽  
Blood Coagulation ◽  
Binding Proteins ◽  
Membrane Binding ◽  
Dependent Manner ◽  
Cellular Regulation ◽  
Membrane Function ◽  
Unique Mechanism ◽  
Ion Conductances

The annexins are a family of Ca2+-dependent membrane binding proteins that have been shown to regulate ion conductances, aggregate vesicles and the cytoskeleton, inhibit phospholipase A2, and inhibit blood coagulation. The annexins represent a unique mechanism of cellular regulation by modifying membrane functions in a Ca2+-dependent manner.

scholarly journals A novel phospholipase A2 from human placenta

1995 ◽  
Vol 311 (1) ◽  
pp. 147-153 ◽  
Author(s):  
W J Buhl ◽  
L M Eisenlohr ◽  
I Preuss ◽  
U Gehring
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Molecular Mass ◽  
Human Placenta ◽  
Type Ii ◽  
Human Term Placenta ◽  
Phospholipases A2 ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipases A2 ◽  
Phospholipase A2 Inhibitors

A major soluble phospholipase A2 of human term placenta was characterized and purified about 15,000-fold to homogeneity. The apparent molecular mass as determined in SDS/polyacrylamide gels is 42 kDa. The enzyme is inhibited by dithiothreitol indicating the presence of disulphide bridges which are essential for activity. Studies with known phospholipase A2 inhibitors revealed no immediate relationship to either secretory or cytosolic phospholipases A2. The placental enzyme prefers liposomes of phosphatidylcholine and has a distinct preference for arachidonic acid in the sn-2 position. It tolerates various detergents. Roughly 10 microM Ca2+ is required for activity, but it cannot be replaced by Mg2+ or Mn2+; Zn2+, Cu2+ and Fe3+ are inhibitory. In immunoblots, the placental enzyme was not detected by two separate antisera specific for type-II phospholipases A2 but reacted very weakly with antisera directed against cytosolic phospholipase A2. From these data we suggest that this enzyme is a novel form of phospholipase A2 which may be involved in arachidonic acid mobilization both during the course of pregnancy and at parturition.

scholarly journals Heparan sulphate inhibition of cell proliferation induced by TGFβ and PDGF

1993 ◽  
Vol 2 (4) ◽  
pp. 299-302
Author(s):  
lan E. Silber ◽  
Jeanine M. Walenga ◽  
Jawed Fareed ◽  
Elizabeth J. Kovacs
Keyword(s):  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Inhibitory Effects ◽  
Dermatan Sulphate ◽  
Future Studies ◽  
Continuous Presence ◽  
Dose Dependent ◽  
Block Growth

The effect of glycosaminoglycans (GAGs) on the proliferation of smooth muscle cells (SMC) and fibroblasts was assessed by culturing cells with or without GAGs. Porcine heparan sulphate (HS) inhibited proliferation in a dose dependent manner. At 167 μg/ml of HS this reached 88% and 72% inhibition of SMC and fibroblast growth, respectively. Pig and beef mucosal heparins also blocked proliferation, but to a lesser extent. In contrast, beef lung heparin, chondroitin sulphate, and dermatan sulphate failed to block growth factor induced proliferation. Continuous presence of HS was not required, suggesting that the inhibitory effects resulted from a direct effect on the cell rather than an interaction of the GAG with growth factors. The mechanism by which GAGs inhibit proliferation will be addressed in future studies.

scholarly journals An IKLLI-containing peptide derived from the laminin α1 chain mediating heparin-binding, cell adhesion, neurite outgrowth and proliferation, represents a binding site for integrin α3β1 and heparan sulphate proteoglycan

1999 ◽  
Vol 340 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Ken-ichiro TASHIRO ◽  
Akira MONJI ◽  
Ichiro YOSHIDA ◽  
Yoshihito HAYASHI ◽  
Kazunori MATSUDA ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Neurite Outgrowth ◽  
Pc12 Cell ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Dependent Manner ◽  
Heparin Binding ◽  
Heparan Sulphate Proteoglycan ◽  
Sulphate Proteoglycan ◽  
Integrin Α3β1

We synthesized and characterized several peptides containing the IKLLI sequence in the α1 chain of laminin-1. The IKLLI-containing peptides, such as LA4 (CSRNLSEIKLLISRARK), LA5 (EIKLLIS) and LA5L (SEIKLLIS), were found to mediate heparin binding and cell adhesion, while also promoting neurite outgrowth in PC12 cells. Furthermore, peptides LA4 and LA5 also mediated proliferation. However, a scrambled peptide, LA5S (ILEKSLI), did not show any of these activities. Anti-LA4 antibodies inhibited laminin- and LA5-mediated cell adhesion and neurite outgrowth, and anti-(integrin α3) and anti-(integrin β1) antibodies inhibited LA5-mediated cell adhesion and neurite outgrowth. Heparin and heparan sulphate inhibited LA5-mediated heparin binding and PC12 cell adhesion in a dose- dependent manner. The IC50 for inhibition of heparin binding and cell adhesion was observed with 9 μM and 8 μM heparin/heparan sulphate respectively. Furthermore, heparan sulphate proteoglycan also inhibited LA5-mediated PC12 cell adhesion with an IC50 of 100 μg/ml. However, chondroitin sulphate (dermatan sulphate) did not inhibit cell adhesion. These data suggest that an IKLLI-containing peptide derived from the laminin α1 chain may be an active site of laminin and that its cell adhesion may thus interact with both integrin α3β1 and cell- surface heparan sulphate proteoglycan.

scholarly journals Urocortin increased endothelial ICAM1 by cPLA2-dependent NF-κB and PKA pathways in HUVECs

2014 ◽  
Vol 52 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Rong Wan ◽  
Yunxin Liu ◽  
Li Li ◽  
Chao Zhu ◽  
Lai Jin ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Time Dependent ◽  
Intercellular Adhesion Molecule ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Intercellular Adhesion Molecule 1 ◽  
Phospholipases A2 ◽  
Cytosolic Phospholipases A2 ◽  
Umbilical Vein Endothelial Cells

Urocortin (Ucn1), a member of the corticotrophin-releasing hormone (CRH) family, has been reported to participate in inflammation. The increased expression of intercellular adhesion molecule 1 (ICAM1) plays important roles in inflammation and immune responses. Our previous results demonstrated that Ucn1 significantly enhanced the expression of ICAM1. However, the underlying mechanisms are still unknown. The purpose of this study is to investigate the detailed mechanisms of Ucn1-induced upregulation of ICAM1. Here, we characterized the mechanisms of Ucn1 usage to regulate ICAM1 expression in human umbilical vein endothelial cells (HUVECs). Our data revealed that Ucn1 increased ICAM1 and cyclooxygenase 2 (COX2) expressions in a time-dependent manner via CRH receptor 2 (CRHR2). In addition, COX2 was involved in ICAM1 upregulation. Furthermore, Ucn1 could increase the expression and phosphorylation of cytosolic phospholipases A2 (cPLA2) in a time-dependent manner via CRHR2 and CRHR1. Moreover, ablation of cPLA2 by the inhibitor pyrrophenone or siRNA attenuated the ICAM1 increase induced by Ucn1. In addition, nuclear factor κB (NF-κB) was activated, indicated by the increase in nuclear p65NF-κB expression and phosphorylation of p65NF-κB, depending on cPLA2 and CRHR2 activation. Pyrrolidinedithiocarbamic acid, an inhibitor of NF-κB, abolished the elevation of ICAM1 but not COX2. Also, Ucn1 increased the production of prostaglandin E2 (PGE2) which further activated protein kinase A (PKA)–CREB pathways dependent of cPLA2 via CRHR2. Moreover, the increase in NF-κB phosphorylation was not affected by the selective COX2 inhibitor NS-398 or the PKA inhibitor H89. In conclusion, these data indicate that Ucn1 increase the ICAM1 expression via cPLA2-NF-κB and cPLA2-COX2-PGE2-PKA-CREB pathways by means of CRHR2.

scholarly journals Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites

2011 ◽  
Vol 2011 ◽  
pp. 1-21 ◽  
Author(s):  
Elizabeth G. Kane ◽  
Andrew W. Taylor-Robinson
Keyword(s):  
Plasmodium Falciparum ◽  
Chondroitin Sulphate ◽  
Specific Binding ◽  
First Trimester ◽  
Effective Vaccine ◽  
Dependent Manner ◽  
Insufficient Information ◽  
Infant Deaths ◽  
Cytokine Balance ◽  
Current Vaccine

Pregnancy-associated malaria, a manifestation of severe malaria, is the cause of up to 200,000 infant deaths a year, through the effects of placental insufficiency leading to growth restriction and preterm delivery. Development of a vaccine is one strategy for control. Plasmodium falciparum-infected red blood cells accumulate in the placenta through specific binding of pregnancy-associated parasite variants that express the VAR2CSA antigen to chondroitin sulphate A on the surface of syncytiotrophoblast cells. Parasite accumulation, accompanied by an inflammatory infiltrate, disrupts the cytokine balance of pregnancy with the potential to cause placental damage and compromise foetal growth. Multigravid women develop immunity towards VAR2CSA-expressing parasites in a gravidity-dependent manner which prevents unfavourable pregnancy outcomes. Although current vaccine design, targeting VAR2CSA antigens, has succeeded in inducing antibodies artificially, this candidate may not provide protection during the first trimester and may only protect those women living in areas endemic for malaria. It is concluded that while insufficient information about placental-parasite interactions is presently available to produce an effective vaccine, incremental progress is being made towards achieving this goal.

scholarly journals Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 603
Author(s):  
Hyunseong Kim ◽  
Jin Young Hong ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
In-Hyuk Ha
Keyword(s):  
Phospholipase A2 ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neurological Diseases ◽  
Minor Component ◽  
Underlying Mechanism ◽  
Bee Venom ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Wide Range

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

Effect of glucocorticoid on prostaglandin F2α-induced prostaglandin E2 synthesis in osteoblast-like cells: inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2

1994 ◽  
Vol 131 (5) ◽  
pp. 510-515 ◽  
Author(s):  
Osamu Kozawa ◽  
Haruhiko Tokuda ◽  
Atsushi Suzuki ◽  
Jun Kotoyori ◽  
Yoshiaki Ito ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase A2 ◽  
Phospholipase C ◽  
Phospholipase A ◽  
Phosphoinositide Hydrolysis ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Kinase C ◽  
Dose Dependent

Kozawa O, Tokuda H, Suzuki A, Kotoyori J, Ito Y, Oiso Y. Effect of glucocorticoid on prostaglandin F2α-induced prostaglandin E2 synthesis in osteoblast-like cells: inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2. Eur J Endocrinol 1994;131:510–15. ISSN 0804–4643 It is well known that osteoporosis is a common complication of patients with glucocorticoid excess. We showed previously that prostaglandin (PG) F2α stimulates the synthesis of PGE2, a potent bone resorbing agent, and that the activation of protein kinase C amplifies the PGF2α-induced PGE2 synthesis through the potentiation of phospholipase A2 activity in osteoblast-like MC3T3-E1 cells. In the present study, we examined the effect of dexamethasone on PGE2 synthesis induced by PGF2α in MC3T3-E1 cells. The pretreatment with dexamethasone significantly inhibited the PGE2 synthesis in a dose-dependent manner in the range between 0.1 and 10 nmol/l in these cells. This effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone also inhibited PGE2 synthesis induced by melittin, known as a phospholipase A2 activator. Furthermore, dexamethasone significantly inhibited the enhancement of PGF2α- or melittin-induced PGE2 synthesis by 12-O-tetradecanoylphorbol-13-acetate, known as a protein kinase C activator. In addition, dexamethasone significantly inhibited PGF2α-induced formation of inositol phosphates in a dose-dependent manner between 0.1 and 10 nmol/l in MC3T3-E1 cells. These results strongly suggest that glucocorticoid inhibits PGF2α-induced PGE2 synthesis through the inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2 in osteoblast-like cells. Osamu Kozawa, Department of Biochemistry, Institute for Developmental Research, Aichi Prefectural Colony, Kasugai, Aichi 480-03, Japan

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