Effects of low doses of thrombin on human platelet phospholipids.
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Animals↗
Biomedical subjects
M Lagarde
Publications and source records attributed to M Lagarde.
Blood cell redox status and fatty acids.
Glutathione-dependent peroxidase (GSH-Px) degrades the deleterious hydroperoxides, including those issued from arachidonic acid (AA) by the action of lipoxygenases, into their alcohol counterpart. We report that the hyperactivity of platelets from elderly people and of polymorphonuclear neutrophils from allergic patients, at least partly due to higher formation of thromboxane A2 and leukotriene B4, respectively, is associated with a depressed GSH-Px activity. As we report that n-3 fatty acids may enhance the cell GSH-Px activity, we conclude that the reduction of cell hyperactivity described in response to those fatty acids might be linked to their effect on GSH-Px.
Aged↗
Differential effects of long chain n-3 fatty acids on the expression of PGH synthase isoforms in bovine aortic endothelial cells.
Primary cultures of bovine aortic endothelial cells were used at confluency to evaluate the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on the expression of both the constitutive and inducible isoforms of PGH synthase (PGHS), PGHS-1 and PGHS-2, respectively. After a 22 h period enrichment of cell lipid stores with each fatty acid, the expression of PGH synthase isoforms was measured by western blotting. EPA and DHA, but not oleate, significantly decreased the immunoreactive PGHS-1 and to a similar extent the corresponding mRNA, as measured by northern blotting. Studies on mRNA stability failed to show any difference between DHA-enriched and control cells, indicating that the decreased expression observed was likely from transcriptional origin. Under the enrichment conditions, EPA and DHA, but not oleate, moderately but significantly induced an oxidative stress as judged by malondialdehyde formation. Interestingly, hydrogen peroxide was able to mimic the effect of EPA and DHA in decreasing the expression of PGHS-1. On the other hand, the PMA-induced PGHS-2 expression could be potentiated by cell pre-enrichment with DHA, whereas hydrogen peroxide alone could induce such an expression. We conclude that the long chain n-3 fatty acids EPA and DHA may differently affect the expression of PGH synthase isoforms, possibly via an oxidative stress.
Animals↗
Impaired microvascular responses to acute hyperglycemia in type I diabetic rats.
Abnormal reactivity of resistance vasculature may induce long-term alterations in regional hemodynamics, contributing to the pathogenesis of diabetic microangiopathy. The purpose of this study was to examine the responses of microvessels to a hyperglycemic episode aimed at mimicking a physiological stimulus such as the postprandial state. This study is the first to report the direct, in situ, visualization of this situation by intravital microscopy in the skeletal muscle of diabetic rat and is particularly interesting as it applies to an iterative, physiological stimulus. The study was conducted in 5-month-old rats, either nondiabetic (ND) or rendered diabetic (D) for 12 weeks (streptozotocin, 60 mg/kg, i.v.). Intravital microscopy was used to examine diameter and vasomotion changes in precapillary arterioles (< 20 microm) in the spinotrapezius muscle of fasted, anesthetized rats, before and up to 60 min after infusion of glucose or isotonic saline. After intravenous glucose infusion, a precapillary arteriolar vasoconstriction associated with an increase in the number of arterioles presenting vasomotion were seen in ND rats. In contrast, no modification in either parameter was observed in D rats. Our results indicate that, microvessels react to acute changes in the metabolic environment such as induced by elevation of plasma glucose. There was a complete loss of reactivity (vasoconstriction and vasomotion) of precapillary arterioles to superimposed hyperglycemia in D rats. According to the "hemodynamic hypothesis", this impaired vasoconstriction could result in hyperperfusion of microvessels and subsequent microvascular damages which might contribute to the development of diabetic microangiopathy.
Animals↗
Platelets mediate the action of diethylcarbamazine on microfilariae.
More than 400 million people in the world are infected by filarial parasites leading to a wide range of pathologies. Although introduced in 1947, the mainstay of the therapy and control of the filariases is diethylcarbamazine (N,N-diethyl-4-methyl-1-piperazine carboxamide; DEC), the mode of action of which still remains unknown despite widespread use and intensive laboratory investigations. The marked contrast between an extremely rapid action in vivo and the absence of any significant activity on microfilariae in vitro is unique among chemotherapeutic agents. DEC has been thought to modify the surface layer of the microfilariae and expose them to immunological cell-mediated lysis. This report provides the first evidence that the effect of DEC is mediated by blood platelets with the additional triggering of a filarial excretory antigen (FEA). The killing mechanism is antibody-independent and involves the participation of free radicals.
Animals↗
Aldehydes from n-6 fatty acid peroxidation. Effects on aminophospholipids.
4-Hydroxy-nonenal (4-HNE) is a major by-product of n-6 fatty acid peroxidation. It has been described to covalently bind biomolecules expressing primary amine, especially the Lys residues in proteins. Low-density lipoproteins (LDL) are well-described macromolecules to be modified by 4-HNE, making them available to scavenger receptors on macrophages. Those macrophages then become foam cells and play an active role in atherogenesis. This paper reports on the covalent binding of 4-HNE to phosphatidylethanolamine (PE), a major aminophospholipid in biological membranes. In contrast, phosphatidylserine (PS) is virtually not modified by 4-HNE. One stable adduct, the Michael adduct PE/4-HNE is a poor substrate of secreted phospholipase A(2) and is not cleaved by phospholipase D. Plasmalogen PE, an important subclass of PE, is covalently modified by 4-HNE as well, but appears to be further degraded on its sn-1 position, the alkenyl chain, which might alter the antioxidant potential of the molecule. An aldehyde homologous to 4-HNE has been characterized as a breakdown product of 12-hydroperoxyeicosatetraenoic acid (12-HpETE) and named 4-hydroxy-2E,6Z-dodecadienal (4-HDDE). This compound as well as 4-HNE was detected in human plasma. Finally, 4-HDDE appears almost 3-fold more active than 4-HNE to make covalent adducts with PE. We conclude that 4-HNE and 4-HDDE are two biologically relevant markers of n-6 fatty acid peroxidation that may alter the phospholipid-dependent cell signaling.
Aldehydes↗
Noninvasive orthogonal polarization spectral imaging as applied to microvascular studies in mice.
In vivo observations of the mouse microcirculation can hardly be performed due to technical difficulties, limiting the knowledge that could be obtained from gene manipulated mice models. The aim of the present study was to check the applicability of a novel optical system, the orthogonal polarization spectral technology, to study the mouse microcirculation. In anaesthetized mice, the spinotrapezius muscle microcirculation was observed in situ. The diameter of precapillary arterioles was measured before and after a pharmacological or hormonal stimulation. High-contrast images of the muscle microcirculation were obtained and significant vasodilatation of arterioles was observed after topical applications of acetylcholine, sodium nitroprusside, and insulin. As compared to conventional techniques, orthogonal polarization spectral imaging makes it possible to assess and study microvascular beds in mice, which were inaccessible until now, allowing the use of gene manipulated mice to investigate, for example, the mechanisms involved in the development of diabetic microangiopathy.
Acetylcholine↗
Mitochondrial H2O2 production is reduced with acute and chronic eccentric exercise in rat skeletal muscle.
Oxidative stress with acute/chronic exercise has been so far examined using exercise involving a combination of concentric and eccentric contractions, but skeletal muscles are likely to be injured to a greater extent by pliometric contractions. In the present study, the effects of acute and chronic bouts of downhill running exercise on mitochondrial hydrogen peroxide (H2O2) generation (fluorimetric detection of a dimer with homovanillic acid in presence of horseradish peroxidase) and oxygen consumption in conjunction with antioxidant enzymes activity were examined. The results show that acute eccentric exercise was accompanied by a significantly reduced mitochondrial H2O2 production that is likely due to a decrease in complex I of the electron transport chain (ETC). On the other hand, eccentric training leads to positive adaptations, reflected by a higher citrate synthase activity and decreased mitochondrial H2O2 production. The decrease in mitochondrial H2O2 cannot be attributed to alterations in antioxidant capacities but rather to changes in mitochondrial membrane composition characterized by an increased polyunsaturated to saturated fatty acids ratio, and decreased contents in arachidonic acid and plasmalogens. These results suggest that changes in mitochondrial membrane properties with eccentric training can affect H2O2 production by muscle mitochondria. It is hypothesized that these changes resulted in a mild uncoupling sufficient to reduce electron back flow through complex I of the ETC, the major generator of reactive oxygen species by skeletal muscle mitochondria.
Animals↗
Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain.
The metabolic fate of docosahexaenoic acid (DHA) was evaluated from its intake as a nutrient in triglycerides and phosphatidylcholines to its uptake by target tissues, especially the brain. Several approaches were used including the kinetics and tissue distribution of ingested 13C-labeled DHA, the incorporation of radiolabeled DHA injected as its nonesterified form compared to the fatty acid esterified in lysophosphatidylcholine (lysoPC), and the capacity of the two latter forms to cross a reconstituted blood-brain barrier (BBB) consisting of cocultures of brain-capillary endothelial cells and astrocytes. The results obtained allow us to raise the hypothesis that lysoPC may represent a preferred physiological carrier of DHA to the brain.
Animals↗
Chernobyl clean-up workers erythrocyte membrane lipid content at the remote period.
Chernobyl Nuclear Power Plant accident clean-up workers were exposed to different radiation doses. Realization of remote effects depends on cellular membrane structure and function. We studied lipid composition of erythrocyte ghost and blood plasma in clean-up workers on the 12-th year after the accident. Groups of Chernobyl accident clean-up workers, non-irradiated patients with the same diseases and healthy controls were studied. Phospholipids were analyzed by two dimentional thin layer chromatography on silica gel. To analyse fatty acids and cholesterol gas chromatography was used. Total cholesterol and total phospholipids amounts in clean-up workers erythrocyte ghost were increased. The level of sphingomyelin and phosphatidylethanolamine raised. In some of the studied irradiated patients lysophosphatidylethanolamine appeared. The distribution of (diacyl)- and plasmalogen forms of phosphatidylcholine and phosphatidylethanolamine was not affected. The fatty acid composition changed slightly except 22:5 n-3, which level significantly increased and 22:5 n-6, which quantity lowered. The unsaturation index remains unchanged. No change in lipid composition of blood plasma was detected. All the changes in lipid composition of erythrocyte ghost of irradiated and unexposed patients were very similar. The obtained results confirm the suggestion about non-specific remote effects after exposure to low doses of ionizing irradiation.
Cholesterol↗
Increased membrane fluidity in blood leukocytes from allergic subjects. A possible role for leukotriene B4.
Modifications of lipid metabolism and increased plasma membrane fluidity may occur during cell activation and occur in leukocytes of patients with allergic disease. Using a fluorescent probe (TMA-DPH) and a polarization technique, we studied the variations of membrane fluidity in blood leukocytes from allergic and normal subjects. The anisotropic coefficient, which is inversely related to the rotational motion of the probe in membrane phospholipids, was significantly higher in normal subjects than in allergic ones. This result implies an increased membrane fluidity in leukocytes from allergic patients. No correlation could be observed with the etiology or the severity of allergic disease, nor with cell preparation composition or serum IgE level. Such a modification of membrane fluidity has been reproduced after incubation of leukocytes from normal subjects with leukotriene B4, but not with cells from allergic patients. Establishing the mechanism of these differences requires further investigations.
Anisotropy↗
The molecular heterogeneity of chronic lymphocytic leukemia: further data.
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Antigens, Surface↗
[Use of intravenous urea in the treatment of the patinful crises of sickle cell anemia].
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Adult↗