Activation of high levels of endogenous phospholipase A2 in cultured cells.

Shier, W. Thomas

doi:10.1073/pnas.76.1.195

Cited by 153 publications

(73 citation statements)

References 25 publications

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“…Qualitatively similar Ca2+-dependent AH activity has also been identified in examinations of plasma membrane fractions prepared from IM (20). These findings are consistent with studies in other tissues which have also demonstrated Ca2+-dependent AH activity associated with microsomes and plasma membranes (4,13,(22)(23)(24). Addition of hypertonic urea to the enzyme assay mixture, suppressed Ca2+-responsive particulate AH of IM (Fig.…”

Section: Discussionsupporting

confidence: 80%

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

Craven¹,

Studer²,

DeRubertis³

1981

J. Clin. Invest.

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A B S T R A C T Previous studies have dlemonstrated that hyperosmolar NaCl and miiannitol stimulate immunoreactive prostaglandin E (iPGE) production by slices of inner medulla (IM), wherease urea inhibits this process. In the present study, the roles of Ca21 and calmodulin in the control of PCE synthesis in IM and the basis for the differential actions of solutes were examined. A23187 increased ['4C]arachidonate (AA) release and iPGE accumulatioin in the presence but not in the absence of media Ca2+ whereas stimulation by hypertonic NaCl or mannitol was well expressed with Ca2+ or in Ca2+-free buffer containing 2 mM EGTA. Hypertonic urea and trifluoperazine (TFP), an inhibitor of actions of the Ca2+-CaM complex, suppressed increases in [14C]AA release and iPGE induced by A23187, NaCl, or mannitol. By contrast, increases in iPGE in response to exogenous AA were not altered by urea or TFP. Ca2+ (25-100 uM) increased acyl hydrolase (AH) activity in EGTA washed (4°C) 100,000g particulate fractions of IM threefold, thereby restoring AH activity to the higher basal values of particulate fractions not washed with EGTA. This action of Ca2+ was blocked by hypertonic urea or TFP, whereas AH activity was not influenced by NaCl or mannitol in the presence or absence of Ca2 . In contrast to their effects on AH activity, hypertonic urea and TFP did not alter conversion of AA to PGE2, PGF2a, or PGD2 by IM microsomal fractions. Ca2+-induced increases in particulate AH were blunted after partial depletion of endogenous CaM-like activity.Ca2+ action was restored by addition of purified exogenous CaM, but not by addition of other small acidic proteins, including troponin C. The findings support a role for CaM in the regulation of PGE synthesis in the IM at the level of Ca2+-responsive AH activity. They further imply that urea suppresses PGE

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Section: Discussionsupporting

confidence: 80%

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

Craven¹,

Studer²,

DeRubertis³

1981

J. Clin. Invest.

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“…It is the major component in the venom of the European honey bee Apis mellifera, has a powerful hemolytic activity [13] and is reported to activate phospholipase A 2 found in the bee venom [14,15]. Furthermore, melittin can induce bilayer fusion [16].…”

Section: Introductionmentioning

confidence: 99%

A molecular dynamics study of the bee venom melittin in aqueous solution, in methanol, and inserted in a phospholipid bilayer

2005

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The structural properties of melittin, a small amphipathic peptide found in the bee venom, are investigated in three different environments by molecular dynamics simulation. Long simulations have been performed for monomeric melittin solvated in water, in methanol, and shorter ones for melittin inserted in a dimyristoylphosphatidylcholine bilayer. The resulting trajectories were analysed in terms of structural properties of the peptide and compared to the available NMR data. While in water and methanol solution melittin is observed to partly unfold, the peptide retains its structure when embedded in a lipid bilayer. The latter simulation shows good agreement with the experimentally derived 3 J-coupling constants. Generally, it appears that higher the stability of the helical conformation of melittin, lower is the dielectric permittivity of the environment. In addition, peptide-lipid interactions were investigated showing that the C-terminus of the peptide provides an anchor to the lipid bilayer by forming hydrogen bonds with the lipid head groups.

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“…In fact, an increase in cPLA 2 activity may occur through mechanisms independent of up-regulation of cPLA 2 expression, e.g., in the intracellular calcium-mediated pathway (25,28,47).…”

Section: Discussionmentioning

confidence: 99%

In Vivo and In Vitro Studies of Cytosolic Phospholipase A₂Expression inHelicobacter pyloriInfection

Nardone¹,

Holicky

Uhl

et al. 2001

Infect Immun

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Modifications of mucosal phospholipids have been detected in samples from patients with Helicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A 2 activity (PLA 2 ). The cytosolic form of this enzyme (cPLA 2 ), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA 2 expression and PLA 2 activity in the gastric mucosae of patients with and without H. pylori infection. In gastric biopsies from 10 H. pylori-positive patients, cPLA 2 levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA 2 activity were higher than in 10 H. pylori-negative gastritis patients. To clarify whether H. pylori had a direct effect on the cellular expression of cPLA 2 , we studied cPLA 2 expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with different H. pylori strains. The levels of cPLA 2 , mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA 2 protein expression was observed in AGS or MKN 28 cells treated with wild-type H. pylori. In conclusion, our study shows increased cPLA 2 expression and PLA 2 activity in the gastric mucosae of patients with H. pylori infection and no change in epithelial cell lines exposed to H. pylori.Helicobacter pylori infection of the gastric mucosa is present worldwide and may be associated with several pathologic alterations, including gastric cancer (30). The relationship between this organism and the development of gastric cancer has been postulated mainly on the basis of epidemiological investigations and animal models of H. pylori infection (13,15,17,21,39,40,53). This relationship is further supported by the finding that some patients with H. pylori infection show the genetic abnormalities of dysplasia and metaplasia in mucosal areas before the development of carcinoma (35, 50). However, the molecular mechanisms underlying the multistep process of gastric carcinogenesis related to H. pylori infection remain undefined (57). It has been shown that H. pylori damages the gastric barrier function and induces a dramatic change in mucosal phospholipid composition (34). This is likely due to a local increase in phospholipase A 2 (PLA 2 ) activity (4, 27). The cytosolic form (cPLA 2 ), but not the secretory form, of this enzyme is involved in cellular signaling and growth (2,25,26,28,31,38,51) and has recently been implicated in the pathogenesis of malignant transformation (11,22,32,48,49,55,56). Furthermore, many human tumors have been reported to exhibit increased synthesis of prostaglandins, the formation of which is dependent on an increase in cPLA 2 activity (16,18,19,29).In this study, we analyzed cPLA 2 expression in gastric-mucosal b...

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Activation of high levels of endogenous phospholipase A2 in cultured cells.

Cited by 153 publications

References 25 publications

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

A molecular dynamics study of the bee venom melittin in aqueous solution, in methanol, and inserted in a phospholipid bilayer

In Vivo and In Vitro Studies of Cytosolic Phospholipase A₂Expression inHelicobacter pyloriInfection

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Activation of high levels of endogenous phospholipase A2 in cultured cells.

Cited by 153 publications

References 25 publications

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

Renal inner medullary prostaglandin synthesis. A calcium-calmodulin-dependent process suppressed by urea.

A molecular dynamics study of the bee venom melittin in aqueous solution, in methanol, and inserted in a phospholipid bilayer

In Vivo and In Vitro Studies of Cytosolic Phospholipase A2Expression inHelicobacter pyloriInfection

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In Vivo and In Vitro Studies of Cytosolic Phospholipase A₂Expression inHelicobacter pyloriInfection