scholarly journals Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes

2020 ◽  
Vol 21 (7) ◽  
pp. 2581 ◽  
Author(s):  
Eric Owusu Obeng ◽  
Isabella Rusciano ◽  
Maria Vittoria Marvi ◽  
Antonietta Fazio ◽  
Stefano Ratti ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Total Phospholipid ◽  
Second Messengers ◽  
Phospholipid Content ◽  
Minor Portion ◽  
Total Phospholipid Content ◽  
Cancer Types ◽  
Regulate Protein ◽  
A Minor ◽  
Pkc Activation

Phosphoinositides (PI) form just a minor portion of the total phospholipid content in cells but are significantly involved in cancer development and progression. In several cancer types, phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] play significant roles in regulating survival, proliferation, invasion, and growth of cancer cells. Phosphoinositide-specific phospholipase C (PLC) catalyze the generation of the essential second messengers diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (InsP3) by hydrolyzing PtdIns(4,5)P2. DAG and InsP3 regulate Protein Kinase C (PKC) activation and the release of calcium ions (Ca2+) into the cytosol, respectively. This event leads to the control of several important biological processes implicated in cancer. PLCs have been extensively studied in cancer but their regulatory roles in the oncogenic process are not fully understood. This review aims to provide up-to-date knowledge on the involvement of PLCs in cancer. We focus specifically on PLCβ, PLCγ, PLCδ, and PLCε isoforms due to the numerous evidence of their involvement in various cancer types.

Mechanical strain-enhanced fetal lung cell proliferation is mediated by phospholipase C and D and protein kinase C

1995 ◽  
Vol 268 (5) ◽  
pp. L729-L738 ◽  
Author(s):  
M. Liu ◽  
J. Xu ◽  
J. Liu ◽  
M. E. Kraw ◽  
A. K. Tanswell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Second Messengers ◽  
Mechanical Strain ◽  
Rat Lung ◽  
Dependent Protein Kinase ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Dependent Protein ◽  
Pkc Activation

The signaling pathways by which intermittent strain (60 cycles/min, 15 min/h) regulates proliferation of mixed fetal rat lung cell in vitro have been investigated. Adenosine 3',5'-cyclic monophosphate (cAMP) content and cAMP-dependent protein kinase (PKA) activity were not affected by strain. The stimulatory effect of strain on DNA synthesis was also not influenced by the cyclic nucleotide-dependent protein kinase inhibitors H-8 or HA-1004, the adenylate cyclase inhibitor SQ-22536, or a PKA inhibitor and cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). In contrast, intracellular concentrations of two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), were dramatically increased after a short period of strain. This increase in second messengers was accompanied by an increased tyrosine phosphorylation of phospholipase C-gamma 1. Phospholipase D activity was also increased by strain. Mechanical strain elicited a shift in the subcellular distribution of PKC activity from cytosol to membranes shortly after the onset of strain. The specific activity of PKC in the membranes increased 6- to 10-fold within 5-15 min and remained increased throughout a 48-h period of intermittent strain. Strain-induced PKC activation and DNA synthesis were blocked by the PKC inhibitors H-7, staurosporine, and calphostin C, as well as by the phospholipase C inhibitor U-73,122. We conclude that mechanical strain of mixed fetal rat lung cells activates phospholipid turnover via phospholipases, followed by PKC activation, which then triggers the downstream events that lead to cell proliferation.

Effect of fetal exposure to gentamicin on phosphate transport in young rat kidney

1993 ◽  
Vol 265 (6) ◽  
pp. F807-F812
Author(s):  
M. Lelievre-Pegorier ◽  
S. Euzet ◽  
C. Merlet-Benichou
Keyword(s):  
Brush Border Membrane ◽  
Rat Kidney ◽  
Total Phospholipid ◽  
Phospholipid Composition ◽  
Cholesterol Content ◽  
Phosphate Transport ◽  
Phospholipid Content ◽  
Postnatal Maturation ◽  
Rat Pups ◽  
Total Phospholipid Content

The renal phosphate (Pi)-transporting capacity normally increases, due to increased carrier system affinity, during the third postnatal week in rats. However, the tubular Pi reabsorption of rat pups born from gentamicin-treated mothers does not increase during this period. This study determines whether exposure to gentamicin in utero selectively alters the postnatal maturation of the carrier affinity for Pi. Pi and glucose transports by proximal tubule brush-border membrane (BBM) were studied. The maximal rate of uptake (Vmax) of Na-Pi cotransport was significantly lower (536 +/- 169 pmol.mg protein-1.10 s-1; n = 6, P < 0.01) in gentamicin-exposed rats than in controls (1,021 +/- 167 pmol.mg protein-1.10 s-1, n = 6), whereas the Michaelis constant (Km) values were the same. Gentamicin exposure had no effect on plasma parathyroid hormone concentration or on BBM glucose transport activity. The total phospholipid content of BBM, their phospholipid composition, cholesterol content, and cholesterol-to-total phospholipid mole ratio were unaltered, suggesting that membrane fluidity was unchanged. The Vmax of BBM alkaline phosphatase was lower in gentamicin-exposed rats than in controls.

Metabolic basis of diethylaminoethoxyhexestrol-induced phospholipid fatty liver

1987 ◽  
Vol 252 (3) ◽  
pp. E375-E379 ◽  
Author(s):  
M. Kubo ◽  
K. Y. Hostetler
Keyword(s):  
Fatty Liver ◽  
Foam Cell ◽  
Total Phospholipid ◽  
Phospholipid Content ◽  
Liver Phospholipid ◽  
Phospholipase A1 ◽  
Total Phospholipid Content ◽  
Metabolic Basis ◽  
First Time

Diethylaminoethoxyhexestrol caused a foam cell lipidosis in humans characterized by phospholipid storage in the liver, spleen, and other tissues, and this represents the first description of acquired lipidosis caused by a drug. It has been proposed that diethylaminoethoxyhexestrol causes phospholipid fatty liver by concentrating in lysosomes and inhibiting phospholipases but it has not previously been possible to measure the intralysosomal concentration of diethylaminoethoxyhexestrol. In this paper we report for the first time the intralysosomal concentration of this drug in rats. After a single oral dose of diethylaminoethoxyhexestrol (100 mg/kg) the intralysosomal concentration was 7.9 mM at 2.5 h, 15.6 mM at 12 h, and 20.9 mM at 24 h, respectively. The total phospholipid content of lysosomes in drug-treated rats increased 1.9-, 6.0-, and 7.6-fold over control at 2.5, 12, and 24 h, respectively. Purified lysosomal phospholipase A1 was strongly inhibited by diethylaminoethoxyhexestrol in vitro. In phospholipid fatty liver, phospholipid accumulation in lysosomes appears to be caused by the presence of diethylaminoethoxyhexestrol in lysosomes at concentrations estimated to be 7.9–20 mM, because drug levels above 1 mM completely block the activity of purified lysosomal phospholipase A1 in vitro.

STUDIES IN PHOSPHOLIPID METABOLISM: I. EFFECT OF GUANIDOACETIC ACID AND CHOLINE ON LIVER PHOSPHOLIPIDS

1964 ◽  
Vol 42 (8) ◽  
pp. 1183-1194 ◽  
Author(s):  
J. Blumenstein
Keyword(s):  
Total Phospholipid ◽  
Phospholipid Metabolism ◽  
Phospholipid Content ◽  
Subsequent Reduction ◽  
Total Phospholipid Content

An attempt was made to produce 'forced methylation' and subsequent reduction of lecithin content of livers of rats fed a semipurified diet. The addition of guanidoacetic acid to the diet of the rats did not alter either the total phospholipid extracted from their livers or the liver lecithin content significantly. This constant pattern was observed whether choline was included in the diet or not. However, in animals fed a diet deficient in choline, the ratio of lecithin and cephalin extracted from their livers was altered, although the total phospholipid content remained constant.

708. Phospholipids in New Zealand dairy products: II. Seasonal variations in the phospholipid content of butter and of milk and cream

1958 ◽  
Vol 25 (2) ◽  
pp. 202-214 ◽  
Author(s):  
A. K. R. McDowell
Keyword(s):  
New Zealand ◽  
Seasonal Variations ◽  
Dairy Products ◽  
Total Phospholipid ◽  
Skim Milk ◽  
Phospholipid Content ◽  
Early Lactation ◽  
Fat Globules ◽  
Total Phospholipid Content

Samples of milk, skim-milk and raw cream from one factory and of pasteurized cream, buttermilk and butter from two factories were taken twice monthly for varying periods for estimation of total phospholipids and (in butter only) of lecithin, cephalin and sphingomyelin.Seasonal variations in the phospholipid contents of milk, skim-milk and raw cream over 13 months probably were due to the greater proportion of small fat globules in autumn (late lactation) milk compared with spring (early lactation) milk.There were regularly recurring seasonal variations in total phospholipid content of the butters over 3 years. Maximum results were found during autumn and minimum results in winter. Lecithin, cephalin and sphingomyelin contents followed the same trends as the total phospholipid contents.Seasonal variations in phospholipid contents of buttermilks and butters were due mainly to variations in the amount of phospholipid per unit of fat in the cream. Differences in butter-making technique had little effect on the proportion of phospholipids from the cream retained in the butter.Average results for total phospholipid content of the products examined were: milk, 0·038% (0·031–0·050%); skim-milk, 0·018% (0·014–0·023%); buttermilk, 0·156% (0·103–0·191%); butter, 0·133% (0·099–0·181%). The average result for percentage of total phospholipid in the fat of the raw creams examined was 0·44% (0·38–0·51%); and in the fat of the pasteurized creams 0·41% (0·35–0·49%). Average weighted results for total phospholipid and for lecithin, cephalin and sphingomyelin contents of butter were 0·139, 0·041, 0·051 and 0·047% respectively.

Effects of centrifugation, storage, and contamination of amniotic fluid on its total phospholipid content.

1980 ◽  
Vol 26 (2) ◽  
pp. 232-234 ◽  
Author(s):  
E J van Voorst tot Voorst
Keyword(s):  
Amniotic Fluid ◽  
Centrifugal Force ◽  
Total Phospholipid ◽  
Phospholipid Content ◽  
Supernatant Fluid ◽  
Different Temperatures ◽  
Relative Centrifugal Force ◽  
Total Phospholipid Content

Abstract The total phospholipid content of the supernatant fluid decreases rapidly with increasing relative centrifugal force when amniotic fluid is centrifuged. Possible explanations for this are discussed. The effect of storage on the total phospholipid content of amniotic fluid at different temperatures and the influence of contamination with blood and meconium are also described.

Thyroid hormones, malnutrition, and biochemical composition of developing rat lung

1982 ◽  
Vol 242 (6) ◽  
pp. E378-E383 ◽  
Author(s):  
J. Ruel ◽  
P. Coulombe ◽  
J. H. Dussault
Keyword(s):  
Thyroid Hormones ◽  
Adult Animal ◽  
Total Phospholipid ◽  
Cell Mass ◽  
Specific Effect ◽  
Phospholipid Content ◽  
Rat Lung ◽  
Neonatal Hypothyroidism ◽  
Total Phospholipid Content ◽  
Developing Rat

We studied the effects of thyroid hormones and malnutrition on protein, DNA, and phospholipid content of the developing rat lung during the first month of life. Neonatal hypothyroidism significantly decreases the lung phospholipid content by 30-45% between 5 and 30 days of age whether the results are expressed per milligram DNA or per gram tissue. Administration of thyroxine for 3 days to hypothyroid rats increases significantly (20%) their total phospholipid content, mainly through its preferential effect on phosphatidylcholine (50% increase). Adult animal response to thyroid hormones is markedly different from that observed in young rats for most parameters examined. In malnourished rats, lung tissue phospholipids are decreased per cell but not per unit cell mass after 11 days of age. These results show that hypothyroidism has a specific effect on lung phospholipids during the neonatal period.

scholarly journals Lipid requirement of the membrane sodium-plus-potassium ion-dependent adenosine triphosphatase system

1975 ◽  
Vol 146 (3) ◽  
pp. 713-722 ◽  
Author(s):  
K P Wheeler ◽  
J A Walker ◽  
D M Barker
Keyword(s):  
Adenosine Triphosphatase ◽  
Specific Activity ◽  
Total Phospholipid ◽  
Kidney Tissue ◽  
Residual Activity ◽  
Fold Increase ◽  
Enzymic Activity ◽  
Partial Purification ◽  
Phospholipid Content ◽  
Total Phospholipid Content

The dependence of the (Na-++K-+)-dependent ATPase (adenosine triphosphatase) (EC 3.6.1.3) on lipid has been examined in a number of different ways, with the use of various preparations from kidney tissue. The main findings were as follows. (1) The ATPase activities of the preparations examined were closely correlated with their total phospholipid content. (2) Extraction of the ATPase with deoxycholate or Lubrol W, combined with suitable salt-fractionation and washing procedures, removed phospholipid, cholesterol and enzymic activity in parallel; but activity was completely lost before all lipid had been removed. (3) The loss of activity could not be attributed to inhibition by residual detergent. (4) No selective removal of any particular phospholipid class by detergent could be detected. (5) Consistent reactivation of the Lubrol-extracted enzymes was obtained by adding dispersions of exogenous phospholipid, but only some, bearing a net negative charge, such as phosphatidylserine and phosphatidylglycerol, were effective. (6) The degree of reactivation was correlated with the amount of residual activity remaining after lipid depletion. (7) Partial purification of the ATPase, giving a 50-fold increase in specific activity, was not accompanied by selective enhancement of any particular class of phospholipid. We conclude that although the ATPase is dependent on phospholipid, only the reactivation results provide evidence for specificity.

Effects of centrifugation, storage, and contamination of amniotic fluid on its total phospholipid content.

1980 ◽  
Vol 26 (2) ◽  
pp. 232-234 ◽  
Author(s):  
E J van Voorst tot Voorst
Keyword(s):  
Amniotic Fluid ◽  
Centrifugal Force ◽  
Total Phospholipid ◽  
Phospholipid Content ◽  
Supernatant Fluid ◽  
Different Temperatures ◽  
Relative Centrifugal Force ◽  
Total Phospholipid Content

Abstract The total phospholipid content of the supernatant fluid decreases rapidly with increasing relative centrifugal force when amniotic fluid is centrifuged. Possible explanations for this are discussed. The effect of storage on the total phospholipid content of amniotic fluid at different temperatures and the influence of contamination with blood and meconium are also described.

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