Perception of disease and its meanings.
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Attitude↗
Biomedical subjects
W H Anderson
Publications and source records attributed to W H Anderson.
Efficacy of salmeterol xinafoate in the treatment of COPD.
STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. INTERVENTIONS: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.
Administration, Inhalation↗
Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial.
This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclomethasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p < or = 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 microg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.
Administration, Inhalation↗
Potentiation of calcium-mediated stimulation of DNA synthesis by ethanol in human and mouse fibroblasts.
Alcohol abuse is a risk factor for cancers of the gastrointestinal tract, and it also can precipitate psoriasis characterized by hyperproliferation of epidermal cells. Because these effects of alcohol may involve stimulation of cell growth, and ethanol (EtOH) was shown to enhance DNA synthesis in mouse fibroblasts and epidermal cells, we conducted a study to determine whether EtOH can also stimulate mitogenesis in human fibroblasts and keratinocytes. In keratinocytes, EtOH had no effects on mitogenesis after shorter (17-hr) treatments, but it partially prevented inhibition of DNA synthesis elicited by longer treatments (3-4 days) with 2 mM calcium (Ca2+), a differentiation-inducing agent. In contrast, treatment of serum-starved zinc-treated (40 microM) human skin fibroblasts with 50-60 mM EtOH for 17 hr resulted in increased DNA synthesis. EtOH-induced DNA synthesis was blocked by 1 mM EGTA, a specific Ca2+ chelator. Despite the presence of 1.8 mM Ca2+ in the cell culture medium, the addition of 1 mM extra Ca2+ (final concentration, 2.8 mM) for 17 hr induced DNA synthesis, presumably mediated by Ca2+ receptors. In eight independent human skin fibroblast lines examined, treatment with EtOH for 46 hr, but not for 17 hr, invariably enhanced the effects of Ca2+ on DNA synthesis, consistent with synergistic stimulation of cell proliferation by EtOH and Ca2+. Neomycin, a Ca2+ receptor agonist, and EtOH also exerted synergistic effects on DNA synthesis after longer (46-hr) treatments. In mouse NIH 3T3 fibroblasts, both EtOH- and Ca2+-enhanced DNA synthesis after 17-hr treatment, but they stimulated cell proliferation only in combination. The results indicate that in human fibroblasts, EtOH can potentiate the longer-term effects of high concentrations of Ca2+ on DNA synthesis whereas, in keratinocytes, EtOH may inhibit Ca2+-induced differentiation.
Animals↗
Phorbol ester stimulation of phosphatidylcholine synthesis requires expression of both protein kinase C-alpha and phospholipase D.
The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) stimulates both the synthesis and phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine (PtdCho). Here, attached and suspended NIH 3T3 fibroblasts as well as variants of the MCF-7 human breast carcinoma cell line expressing PKC-alpha and a PtdCho-specific PLD activity at widely different levels were used to determine the possible role of PKC-alpha, PtdCho hydrolysis, and choline uptake in the mediation of PMA effect on PtdCho synthesis. In wild-type MCF-7 cells, which express both PKC-alpha and PLD activities at very low levels, PMA had little effects on the uptake or incorporation [14C]choline into PtdCho. In multidrug resistant MCF-7/MDR1 cells, which highly express PKC-alpha but lack the PtdCho-specific PLD activity, 100-nM PMA had relatively small stimulatory effects on the uptake of [14C]choline (approximately 1.5-fold) and [14C]PtdCho synthesis (1.5- to 2-fold). In NIH 3T3 fibroblasts and MCF-7/PKC-alpha cells, both expressing PKC-alpha and PLD activities at high levels, 10-100-nM PMA enhanced [14C]choline uptake only slightly (1.7- to 2.2-fold), while it had much greater (approximately 4-9-fold) stimulatory effects on PtdCho synthesis. PMA significantly enhanced the formation of phosphatidic acid (PtdOH) in MCF-7/PKC-alpha cells (2.8-fold increase), but not in MCF-7/MDR1 cells (1.4-fold increase), while in both cell lines it had only small (1.3-1.5-fold) stimulatory effects on 1,2-diacylglycerol (1, 2-DAG) formation. In suspended NIH 3T3 cells, 200-300-mM ethanol blocked the stimulatory effect of PMA on PtdOH formation without affecting PtdCho synthesis indicating that neither PtdOH nor 1,2-DAG derived from it is a mediator of PMA effect on PtdCho synthesis. In attached NIH 3T3 cells, dimethylbenz[a]anthracene enhanced phosphocholine formation and, thus, choline uptake without increasing PtdCho synthesis or modifying the effect of PMA. While the results indicate that the stimulatory effect of PMA on PtdCho synthesis requires the expression of both PKC-alpha and a PtdCho-specific PLD, they do not support a role for 1,2-DAG, PtdOH or choline in the mediation of PMA effect.
3T3 Cells↗
Ethanol potentiates the stimulatory effects of insulin and phosphocholine on mitogenesis by a zinc-dependent and rapamycin-sensitive mechanism in fibroblasts and JB6 cells.
In most cellular systems ethanol inhibits growth factor-induced cell growth. Here we examined the effects of ethanol on DNA synthesis and cell proliferation induced by insulin and phosphocholine (PCho) in NIH3T3 fibroblasts, Swiss 3T3 fibroblasts and mouse epidermal JB6 cells. In serum-starved low (12-18) passage NIH3T3 fibroblasts, 60 mM ethanol enhanced the mitogenic effect of insulin in the absence or presence of 25 microM zinc about 2- or 12-fold, respectively. In contrast, in serum-starved high (30-47) passage NIH3T3 cells 60 mM ethanol had large (20-40-fold) potentiating effects on insulin-induced DNA synthesis even in the absence of zinc. Furthermore, ethanol also enhanced the effects of PCho on DNA synthesis in both the absence and presence of insulin. The potentiating effects of ethanol on insulin- and PCho-induced DNA synthesis were associated with 1.2-1.3-fold stimulation of cell proliferation. Rapamycin, an inhibitor of p70 S6 kinase action, strongly inhibited the potentiating effects of ethanol on insulin- and PCho-induced mitogenesis. Unexpectedly, ethanol inhibited synergistic activation of p42/p44 mitogen-activated protein kinases by insulin and PCho. In both Swiss 3T3 and JB6 cells, ethanol potentiated insulin-induced DNA synthesis only in the presence of zinc. In these cells, ethanol also increased the effects of PCho on both DNA synthesis and cell proliferation in the co-presence of either insulin or ATP. The results indicate that in various cell lines physiologically relevant concentrations of ethanol can increase the ability of insulin and PCho to induce DNA synthesis and, to smaller extents, cell proliferation. In low passage NIH3T3 cells as well as in Swiss 3T3 and JB6 cells potentiation of insulin-induced DNA synthesis by ethanol requires the presence of zinc.
3T3 Cells↗
Extracellular sphingosine 1-phosphate stimulates formation of ethanolamine from phosphatidylethanolamine: modulation of sphingosine 1-phosphate-induced mitogenesis by ethanolamine.
In this work, we determined the effects of sphingosine 1-phosphate (S1P) on phospholipase D (PLD)-mediated hydrolysis of phosphatidylethanolamine (PtdEtn), and evaluated the effects of the water-soluble product ethanolamine on S1P-induced DNA synthesis in NIH 3T3 cells. In [14C]ethanolamine-labelled cells, S1P (0.5-5 microM) stimulated PLD-mediated hydrolysis of PtdEtn 1.5-2.1-fold. Down-regulation of protein kinase C by chronic (24 h) treatment of cells with 300 nM PMA, or pretreatments (10 min) with the cell-permeant calcium chelator 1,2-bis-(O-aminophenoxy)-ethane-N,N, N',N'-tetra-acetic acid tetra-acetoxymethyl ester led to the inhibition of S1P-induced PtdEtn hydrolysis. S1P alone was a weak inducer of DNA synthesis, but its effects were enhanced by phosphocholine (PCho), insulin, ATP or PMA. Ethanolamine (5-100 microM) did not modify the mitogenic effect of S1P alone, whereas at 50-100 microM concentrations it actually enhanced the mitogenic effect of PCho via a mitogen-activated protein (MAP) kinase-independent mechanism. In contrast, 5-20 microM concentrations of ethanolamine, which correspond to normal blood ethanolamine levels in humans, strongly inhibited DNA synthesis induced by S1P plus PCho via a MAP kinase-dependent mechanism; importantly, less or no inhibition was observed with 50-100 microM concentrations of ethanolamine. At 5-50 microM concentrations, ethanolamine also inhibited the synergistic mitogenic effects of both S1P plus insulin (22-27% inhibition) and PCho plus ATP (45-73% inhibition) but not those of S1P plus PMA or S1P plus ATP. The results indicate that S1P stimulates PLD-mediated hydrolysis of PtdEtn by a mechanism that may involve a regulatory protein kinase C isoform. Increased formation of ethanolamine by PLD-mediated PtdEtn hydrolysis or by other means may be required for maximal stimulation of DNA synthesis by S1P in the presence of insulin, and particularly PCho.
3T3 Cells↗
ATP-dependent choline phosphate-induced mitogenesis in fibroblasts involves activation of pp70 S6 kinase and phosphatidylinositol 3'-kinase through an extracellular site. Synergistic mitogenic effects of choline phosphate and sphingosine 1-phosphate.
In serum-starved NIH 3T3 clone 7 fibroblasts, choline phosphate (ChoP) (0.5-1 mM) and insulin synergistically stimulate DNA synthesis. Here we report that ATP also greatly enhanced the mitogenic effects of ChoP (0.1-1 mM) both in the absence and presence of insulin; maximal potentiating effects required 50-100 microM ATP. The co-mitogenic effects of ATP were mimicked by adenosine 5'-O-(3-thiotriphosphate), adenosine 5'-O-(2-thiodiphosphate), ADP, and UTP, but not by AMP or adenosine, indicating the mediatory role of a purinergic P2 receptor. Externally added ChoP acted on DNA synthesis without its detectable uptake into fibroblasts, indicating that ChoP can be a mitogen only if it is released from cells. Extracellular ATP (10-100 microM) induced extensive release of ChoP from fibroblasts. ChoP had negligible effects, even in the presence of ATP or insulin, on the activity state of p42/p44 mitogen-activated protein kinases, while in combination these agents stimulated the activity of phosphatidylinositol 3'-kinase (PI 3'-kinase). Expression of a dominant negative mutant of the p85 subunit of PI 3'-kinase or treatments with the PI 3'-kinase inhibitor wortmannin only partially (approximately 40-50%) reduced the combined effects of ChoP, ATP, and insulin on DNA synthesis; in contrast, the pp70 S6 kinase inhibitor rapamycin almost completely inhibited these effects. ATP and insulin also potentiated, while rapamycin strongly inhibited, the mitogenic effects of sphingosine 1-phosphate (S1P). Furthermore, even maximally effective concentrations of ChoP and S1P synergistically stimulated DNA synthesis. The results indicate that in the presence of extracellular ATP and/or S1P, ChoP induces mitogenesis through an extracellular site by mechanisms involving the activation of pp70 S6 kinase and, to a lesser extent, PI 3'-kinase.
3T3 Cells↗
Inhibition of phorbol ester-stimulated phospholipase D activity by chronic tamoxifen treatment in breast cancer cells.
We have shown that in an estrogen receptor-negative multidrug-resistant subline of MCF-7 human breast carcinoma cells longer-term (24 h), but not shorter-term (30 min), treatments with clinically relevant (2-5 microM) concentrations of tamoxifen (TAM) inhibited phorbol ester-stimulated phospholipase D (PLD) activity by 50-80%. TAM caused these inhibitory effects without inducing membrane translocation or down-regulation of protein kinase C-alpha, the major mediator of phorbol ester effects on PLD activation. The results raise the possibility that prolonged inhibition of the protein kinase C-alpha-regulated PLD system may contribute to the cytotoxic effects of tamoxifen in estrogen receptor-negative breast cancer cells.
3T3 Cells↗
Lipid differentiation in MP26 junction enriched membranes of bovine lens fiber cells.
The present study was undertaken to address the question whether lipid differentiation occurs in junctional domains which could imply a functional requirement for specific lipids in junctional structures. Junction enriched membranes were isolated from bovine lens fiber cells using Tris and urea treatment, and the presence of junctional structures was ascertained by electron microscopy. Enrichment in major intrinsic protein (MIP, MP26) was monitored by SDS polyacrylamide gel electrophoresis. Junctional lipids were extracted by a modified Folch procedure, to quantitatively recover cholesterol, and lipid classes were analyzed. While 99.5% of total lens protein was solubilized in the course of junction isolation, 43.9% of cell phospholipids (PL) and 64.1% of cell cholesterol (Chol) were conserved. Cholesterol was by far the predominant lipid in the junction enriched lens fiber cell membranes (833 nmol/mg protein) and was more abundant than all phospholipids combined (682 nmol/mg protein). In isolating the junctional membranes, cholesterol levels increased 144-fold, and average phospholipid levels increased 99-fold, which resulted in an increase in Chol/PL ratio from 0.84 to 1.22. Different phospholipids showed substantially different degrees of enrichment with highest enrichments seen for the phosphatidylethanolamine fraction (152-fold) and sphingomyelin (101-fold). Thus, the phospholipids of the junction enriched membranes consisted mainly of ethanolamine glycerophospholipids (37.3%) and sphingomyelin (28.6%), with lesser amounts of choline glycerophospholipids (23.5%) and phosphatidylserine (9.2%) present. Our data suggest that the MP26 junction enriched membranes of bovine lens fiber cells contain differentiated lipid domains, and that cholesterol, ethanolamine glycerophospholipids and sphingomyelin are the prevalent boundary lipids of the major intrinsic protein in these domains.
Animals↗
Mast cell TNF mRNA expression in nasal mucosa demonstrated by in situ hybridization: a comparison of mast cell detection methods.
We have used 35S-labelled RNA probes to detect TNF cytokine gene expression in nasal mucosa derived from patients with perennial rhinitis. As mast cells comprise a minor component of the total cell population in nasal mucosa, additional methods are needed to determine whether mast cells contribute to the cytokine mRNA detected by in situ hybridization. We have combined in situ hybridization with alternate methods to detect mast cells (tryptase immunostaining or toluidine blue staining) and determined that in situ hybridization coupled with tryptase immunostaining provides optimal methods to detect mast cell cytokine gene expression in tissue sections. Using in situ hybridization and tryptase immunostaining, we demonstrate that mast cells in nasal mucosa can express TNF mRNA. However, the number of tryptase-, TNF+ cells (1.99 +/- 1.59 cells/mm2) exceeded the number of tryptase+, TNF+ mast cells (0.09 +/- cells/mm2). Mast cells thus comprised a subpopulation of the total number of TNF mRNA positive cells in nasal mucosa.
Adult↗
Fentanyl patches left on dead bodies -- potential source of drug for abusers.
We report a fatal case of fentanyl poisoning in which the decedent apparently obtained the drug from a used transdermal patch removed from a deceased nursing home patient. Fentanyl drug patches, even those previously used, contain a potentially lethal amount of this potent narcotic analgesic and provide a source of fentanyl for drug abusers. This case demonstrates the importance of proper disposal of these drug patches and the need for strict policies and guidelines in patient care settings regarding their disposal. Since fentanyl derivatives may not be detected on routine toxicologic analysis, specific assays should be utilized for the detection of fentanyl in cases of suspected drug overdose.
Administration, Cutaneous↗
The bisindolylmaleimide GF 109203X, a selective inhibitor of protein kinase C, does not inhibit the potentiating effect of phorbol ester on ethanol-induced phospholipase C-mediated hydrolysis of phosphatidylethanolamine.
In fibroblasts, the protein kinase C (PKC) activator phorbol 12-myristate (PMA) either inhibits or stimulates phospholipase C-mediated hydrolysis of phosphatidylethanolamine in the absence or presence of ethanol, respectively. Here, we demonstrate that the specific PKC inhibitor bisindolylmaleimide GF 109203X prevents only the inhibitory, but not the stimulatory, PMA effect.
3T3 Cells↗
Bilayer nanotubes and helical ribbons formed by hydrated galactosylceramides: acyl chain and headgroup effects.
The molecular basis of bilayer tubule formation in hydrated galactosylceramide (GalCer) dispersions has been investigated by synthesizing different chain-pure GalCers and examining their aqueous mesomorphic phase structure by freeze fracture and negative-stain electron microscopy. Thermotropic characterization of the GalCer species by differential scanning calorimetry provided supplementary information that verified the phase state under which morphological observations were carried out. Under aqueous conditions and at room temperature, N-24:1 delta 15(cis) GalSph, the predominant monounsaturated, nonhydroxy acyl species of bovine brain GalCer (NFA-GalCer), formed cylindrical mesomorphic self-assemblies consisting almost exclusively of "nanotubes," i.e., lipid bilayer tubules of relatively uniform length and diameter (length, 250-400 nm; diameter, 25-30 nm). In contrast, N-24:0 GalSph, the major saturated, nonhydroxy acyl species of bovine brain GalCer, displayed no tendency to form these relatively small "nanotubes." Rather, N-24:0 GalSph formed larger, variable-length ribbon-like structures (length, 5,000-10,000 nm) that often appeared to undulate and, occasionally, appeared to be helically twisted. Interestingly, bovine brain GalCer, which contains high levels of the N-24:1 delta 15(cis) and N-24:0 species as well as 2-hydroxy acyl chains, formed multilamellar liposomes of variable size and showed little tendency to form cylindrical structures. This result suggested that changes to the polar interface/headgroup region imparted by the 2-hydroxy acyl species strongly influenced bilayer tubule and cylinder formation in GalCer. To define this influence more clearly, other sphingoid-based and glycerol-based lipids were investigated. Morphological characterization of N-24:1 delta 15(cis) sphingosylphosphorylcholine (24:1 SM) revealed no evidence of bilayer cylinder or tubule formation. Similar results were obtained with aqueous dispersions of 1-palmitoyl-2-nervonoyl phosphatidylcholine (16:0, 24:1 PC). Hence, the bulkier, more hydrated, zwitterionic phosphocholine headgroup inhibited the formation of bilayer nanotubes and cylinders under physiological saline conditions.
Animals↗
Macro-ripple phase formation in bilayers composed of galactosylceramide and phosphatidylcholine.
As determined by freeze fracture electron microscopy, increasing levels of bovine brain galactosylceramide (GalCer) altered the surface structure of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers by inducing a striking "macro-ripple" phase in the larger, multilamellar lipid vesicles at GalCer mole fractions between 0.4 and 0.8. The term "macro-ripple" phase was used to distinguish it from the P beta' ripple phase observed in saturated, symmetric-chain length phosphatidylcholines. Whereas the P beta' ripple phase displays two types of corrugations, one with a wavelength of 12-15 nm and the other with a wavelength of 25-35 nm, the macro-ripple phase occurring in GalCer/POPC dispersions was of one type with a wavelength of 100-110 nm. Also, in contrast to the extended linear arrays of adjacent ripples observed in the P beta' ripple phase, the macro-ripple phase of GalCer/POPC dispersions was interrupted frequently by packing defects resulting from double dislocations and various disclinations and, thus, appeared to be continuously twisting and turning. Control experiments verified that the macro-ripple phase was not an artifact of incomplete lipid mixing or demixing during preparation. Three different methods of lipid mixing were compared: a spray method of rapid solvent evaporation, a sublimation method of solvent removal, and solvent removal using a rotary evaporation apparatus. Control experiments also revealed that the macro-ripple phase was observed regardless of whether lipid specimens were prepared by either ultra-rapid or manual plunge freezing methods as well as either in the presence or absence of the cryo-protectant glycerol. The macro-ripple phase was always observed in mixtures that were fully annealed by incubation above the main thermal transition of both POPC and bovine brain GalCer before rapid freezing. If the GalCer mixed with POPC contained only nonhydroxy acyl chains or only 2-hydroxy acyl chains, then the occurrence of macro-ripple phase decreased dramatically.
Animals↗
Selective down-regulation of protein kinase c-epsilon by carcinogens does not prevent stimulation of phospholipase D by phorbol ester and platelet-derived growth factor.
It is well established that activators of protein kinase C (PKC) also enhance the activity of phospholipase D (PLD), and that this regulatory mechanism is altered in transformed cells. Here we used the C3H/10T1/2 mouse embryo fibroblast line, a cellular model for the study of carcinogenesis, to examine possible effects of carcinogens on the PKC isoenzyme pattern and on the regulation of PLD by the PKC activators phorbol 12-myristate 13-acetate (PMA) and platelet-derived growth factor (PDGF). Treatment of these fibroblasts with 0.5 microgram/ml 7,12-dimethyl-benz[a]anthracene or benzo[a]pyrene for 24 h greatly decreased (> 80%) the amount of immunoreactive PKC-epsilon. Of the remaining three isoenzymes identified, carcinogens alone had no effect on the cellular status of PKC-alpha and PKC-delta, although they appeared to promote slightly PMA-induced membrane translocation of the cytosolic forms of these isoenzymes in exponentially growing cells. Carcinogens and/or PMA had no effects on the cellular content or distribution of PKC-zeta. Chronic (24 h) treatments with carcinogens resulted in increased or decreased release of [14C]ethanolamine or [14C]choline from the appropriate prelabelled phospholipids, respectively. However, carcinogens failed to block the stimulatory effects of PMA and PDGF on the hydrolysis of phosphatidylethanolamine and phosphatidylcholine or on the synthesis of phosphatidylethanol mediated by PLD. These data indicate that in fibroblasts PKC-epsilon is not a major regulator of PLD activity.
9,10-Dimethyl-1,2-benzanthracene↗
Hydrogen peroxide regulates phospholipase D-mediated hydrolysis of phosphatidylethanolamine and phosphatidylcholine by different mechanisms in NIH 3T3 fibroblasts.
A major goal of this work was to determine in NIH 3T3 fibroblasts whether the recently described effects of H2O2 on phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) are mediated by similar or different mechanisms. While exposure of NIH 3T3 fibroblasts to H2O2 stimulated the hydrolysis of both PtdEtn and PtdCho, the following important differences were noted: (i) prolonged (24 h) treatment of fibroblasts with 400 nM phorbol 12-myristate 13-acetate (PMA) blocked the stimulatory effect of H2O2 on PtdEtn, but not on PtdCho, hydrolysis; (ii) PMA-induced hydrolysis of PtdEtn, but not PtdCho, was inhibited by H2O2; (iii) the stimulatory effect of H2O2 was additive with that of sphingosine or staurosporine, inhibitors of protein kinase C, on the hydrolysis of PtdCho, but not PtdEtn; (iv) with membranes isolated from H2O2-treated fibroblasts, the hydrolysis of PtdCho, but not PtdEtn, was increased compared to values obtained with control membranes. These results imply that H2O2 regulates PtdEtn and PtdCho hydrolysis by different mechanisms. Stimulation of PtdEtn hydrolysis by H2O2, sphingosine, and staurosporine may commonly involve, at least in part, neutralization of an inhibitory protein kinase C isozyme.
3T3 Cells↗