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PubMedDate not supplied

[Opposite effect of lipofuscin granules and melanosomes from human retinal pigment epithelium of eye on photooxidation of cardiolipin].

The influence of lipofuscin granules and melanosomes from human retinal pigment epithelium on the light-induced photooxidation of cardiolipin liposomes and the generation of superoxide radicals was studied. Lipofuscin granules were able to stimulate, while melanosomes inhibited, the cardiolipin photooxidation. The visible light irradiation of both melanosomes and lipofuscin granules generated superoxide radicals with mean rates of 1.5 nmole/min/10(7) and 38 nmole/min/10(7) granules, accordingly. However, melanosomes but not lipofuscin granules reacted readily with superoxide radicals. Moreover, the rate constant of degradation of superoxide radicals in the presence of melanosomes was about five orders of magnitude higher than the rate constant of its photogeneration. Therefore, we propose that melanosomes in retinal pigment epithelium cells have a photoprotective role whereas lipofuscin granules may stimulate photodestructive reactions.

Adult↗

PubMed1992

Relationship between cardiolipin content and cytochrome c oxidase activity of cytochrome aa3 in Paracoccus denitrificans.

Using cultivation at different oxygen tensions, the molar ratio of cardiolipin to haem a in cells of Paracoccus denitrificans was varied systematically from 30 to 300. The molecular activity of cytochrome aa3 (with N, N, N', N'-tetramethyl-p-phenylenediamine as substrate) remained unchanged in this interval, this ruling out any regulatory effect of physiological cardiolipin levels on the terminal oxidase. Titration of anaerobically grown cells with cyanide indicated the presence of cytochrome aa3 which accounted for about 1/4 of the total electron flow from TMPD to oxygen.

Aerobiosis↗

PubMed1956

Use of synthetic, crystalline, L-alpha-dimyristoyl lecithin in cardiolipin antigens.

Experiments were carried out by the authors to determine whether synthetic, crystalline, L-alpha-dimyristoyl lecithin could replace natural purified lecithins in the preparation of cardiolipin antigens. These experiments were designed specifically to find out whether it was possible to obtain the same serological reactions, qualitatively and quantitatively, with the test antigen as with a reference antigen containing natural lecithin, and whether the test antigen had the same keeping qualities as the reference antigen.The tests used were the quantitative complement-fixation test as modified by Mørch in 1933, and the VDRL slide flocculation test.The results showed that synthetic, crystalline, L-alpha-dimyristoyl lecithin could replace natural lecithin in the preparation of cardiolipin antigens, but that the antigens prepared with the synthetic lecithin were significantly less sensitive than those prepared with an equimolar amount of natural lecithin. The authors consider that further investigation is required before the use of synthetic lecithin is finally adopted.

Cardiolipins↗

PubMed1959

Third International Reference Preparation of cardiolipin with special reference to its use in improved serological tests for treponematoses.

The Third International Reference Preparation of Cardiolipin was produced (in a quantity of 2400 ml) at the WHO Serological Reference Centre, Copenhagen, and assayed in 1957 against the Second International Reference Preparation by four laboratories in three countries. Complement-fixation and slide flocculation tests were used. The new preparation was found acceptable, and its establishment was authorized by the WHO Expert Committee on Biological Standardization.The average log(10) titres and results of analyses of variances are shown. The variances were of the usual order of magnitude, and the differences in titre between antigens containing the Second and the Third International Reference Preparations varied from -0.004 to 0.059; only two of the differences exceeded the 5% limit of significance.The use of the Third International Reference Preparation in tests for the acceptability of any new cardiolipin preparation is described.

Biological Assay↗

PubMed1959

Reactivity of a lecithin-free cardiolipin preparation (cardchol) in leprosy sera.

Previous experiments have shown that a mixture of cardiolipin and cholesterol in absolute ethanol (named "cardchol") might be used as an antigen in complement-fixation tests. The reactivity in the complement-fixation test of CWRM (an "ordinary" cardiolipin antigen) was compared with that of cardchol in several experiments, and it could be demonstrated that the reactivity of cardchol was especially pronounced in sera from false-positive reactors. In about 50% of such cases, quantitative determination of the antibody content showed that cardchol was more reactive than CWRM, whereas in syphilitic cases the reactivity of cardchol was inferior to that of CWRM. An exception was primary syphilis, which showed a reactivity level with cardchol equal to or even superior to that of CWRM.Examinations of a certain number of sera from leprosy patients had shown them to be highly reactive with cardchol and non-reactive or weakly reactive with CWRM; this observation is fully confirmed by examination of a larger number of leprosy sera, on which this paper reports. These sera were examined with a battery of tests using lipoidal antigens and with the TPI test. Testing with cardchol proved to give the highest reactivity with these sera, which were mostly non-treponemal.Subdivision of the material according to the clinical stage of leprosy showed that the highest reactivity of cardchol occurred in patients with lepromatous leprosy, particularly in those with leprosy of relatively short duration.Electrophoretic fractionation of these sera demonstrated that the substances reacting with cardchol were situated in the gamma-globulin or gamma- and beta-globulin serum fractions.

Antibodies↗

PubMed1992

A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene.

We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.

Amino Acid Sequence↗

PubMed2006

A novel cationic cardiolipin analogue for gene delivery.

The optically active R and S isomers of cationic cardiolipin analogues (CCA) were synthesized and evaluated as a liposome based transfection reagent. Both isomers form stable liposomes with mean diameters of about 120 nm without any additional lipid ingredients. No significant change in particle size distribution profile was observed over one-month storage at room temperature (20-25 degrees C). The gel to liquid crystalline phase transition temperature (Tm) of cationic liposomes comprised of both R and S isomers was approximately 2 degrees C, as measured by differential scanning calorimetry (DSC). Both isomers also formed stable liposomes when combined with DOPE. In vitro transfection efficiency of the CCA/DOPE liposomes complexed to plasmid DNA was evaluated using a luciferase reporter gene. Both liposomes composed of R and S isomers of the cationic cardiolipin displayed higher transfection efficiency than commercially available Lipofectin. Further in vivo studies are warranted.

Animals↗

PubMedDate not supplied

Correlation between trimester of fetal wastage and anti-cardiolipin antibody titer.

The existence of circulating lupus anticoagulant and anti-cardiolipin antibodies (ACA) has been reported to be associated with recurrent fetal loss. We used an enzyme-linked immunosorbent assay (ELISA) for detection of ACA in plasma samples from 104 women with a history of recurrent fetal loss. The normal range of the ACA level was defined as less than 6 GPL (IgG anti-cardiolipin) units (n = 100 normal plasma samples). Nine women (9.7%) were positive for ACA. The population was divided into two groups on the basis of medical history, and analysis revealed that 42.8% (3/7) of the group of patients with at least one fetal loss in the second or third trimester were positive for ACA; their mean ACA titer was 34 GPL units.

Abortion, Spontaneous↗

PubMedDate not supplied

[The dynamics of antibodies with IgD-class cardiolipin and treponemal group specificity in syphilis assessed quantitatively by radial immunodiffusion].

150 sera (positive at the VDRL, ELISA-Reiter, FTA-ABS tests) were tested by IDRS for the IgD quantification in syphilis. They were collected from men, 25-45 years old, in different stages of the disease, treated or not. The reference normal values for the seric IgD were established on 154 sera taken from men, 25-45 years old, apparently healthy: 0-131.2 UI/ml, with an average of 29.92 +/- 29.61 UI/ml. The IgD values with cardiolipin or group treponemal specificity were obtained from the difference between the values of the immunodiffusion diameters produced by sera, before and after the complete absorbtion with VDRL antigen or delipidated treponemal suspension. The individual values for each serum, mean +/- SD, and the percent values against the total IgD, for each stage of the disease were calculated. The medium levels of the total IgD range within normal limits, except for epsilon 2, where they are considerably higher than normal (52.53 +/- 26.66 UI/ml). All the individual minimal values, between 7.09 and 14.89 UI/ml, are higher than the normal minimal values, under 3.54 UI/ml. Treponemal IgD are present in all the sera in all stages of the disease and the cardiolipin IgD are completely absent. The mean values of the treponemal IgD are about 7-9 UI/ml, with a maximum of 19.3 UI/ml in epsilon 2. A higher percent of treponemal IgD is found, around 30%, with a maximum of 36.7% in epsilon 2. The high percent of the treponemal IgD in epsilon latent and epsilon treated persistent positive shows a continuous activation of the circulating B lymphocytes by the treponemal antigens and therefore an active infectious process. The exclusive presence of the treponemal IgD in all the cases of syphilis, irrespective of the evolution stages, indicated the extremely specific diagnosis value of their detection.

Adult↗

PubMedDate not supplied

[Aggregation of cardiolipin liposomes induced by monovalent cations].

Monovalent ion induced aggregation of the cardiolipin bilayer liposomes is studied. Derived threshold concentrations (Ck) stimulating fast aggregation testify that the order of effectiveness for monovalent cations to cause this process is: H+ greater than Na+ greater than Li+ greater than K+. The Ck is shown to be nonmonotonously dependent on the temperature discovering a maximum in the range approximately 30-40 degrees C. It is also shown that the liposomes preliminary temperature processing for two hours at approximately 70 degrees C as well as the liposomes incubation for several days at approximately 5 degrees C affect the Ck value. In both cases a considerable Ck increase is accompanied by almost two-fold increase of the lipid oxidation index. The studied process is reversible to both electrolyte concentration dilution and temperature changes. However, unlike the phosphatidylserine (PS) and phosphatidic acid (PA) liposomes the observed changes in the cardiolipin case proceeding considerably slower possibly indicate that the potential must be lower in its depth than that in the case of PS and/or PA.

Cardiolipins↗

PubMedDate not supplied

[Anti-cardiolipin antibodies in lupus erythematosus].

Anti-cardiolipin antibodies (ACA) were investigated in the serum of 79 patients with lupus erythematosus by means of ELISA method. 34 patients (43%) had ACA in their serum. 63.6% of the patients with ACA had 4 or more ARA criteria and 75% of them had malar rash. None of our patients had the "anti-cardiolipin antibodies syndrome" but three of them with thrombocytopenia had ACA.

Adult↗

PubMed1987

[Study of complex lipids. Synthesis of diphosphatidylglycerol (cardiolipin) with unsaturated fatty acid residues].

Diphosphatidylglycerol (cardiolipin) with different fatty acid residues has been synthesised by condensation of 1,2-diacyl-sn-glycero-3-phosphoric acid (obtained, e.g., by the cabbage phospholipase D cleavage of 1,2-dioleyl-sn-glycero-3-phosphocholine or egg phosphatidylcholine) with 2-O-tert-butyldimethylsilylglycerol in the presence of 2,4,6-triisopropylbenzenesulphonylchloride. The synthetic cardiolipins as unsonicated aqueous calcium-free dispersions were shown, by means of 31P NMR spectroscopy, to form aggregates of the bilayer structure.

Cardiolipins↗

PubMed1986

The cardiolipin antigen: chemistry and composition.

Cardiolipin, the primary lipid hapten in the antigen suspension used for the detection of antitreponemal antibodies in the sera of syphilitic patients, was successfully coupled to glucose oxidase, peroxidase, and some other enzymes using different crosslinking agents. These complexes were used to replace the pure uncomplexed cardiolipin for the preparation of the antigen suspension. When these suspensions were allowed to react with serum that contained anticardiolipin antibodies the activity of the enzyme was inhibited. In the absence of antibody, no enzyme inhibition was observed.

Antibodies, Bacterial↗

PubMed1982

Purification of cardiolipin for surface pressure studies.

Thin-layer chromatography and surface pressure-area isotherms of commercial bovine cardiolipins showed that the samples contained contaminants. They were purified by TLC and their purity was checked by chromatography and by their monolayer properties. The molecular area of cardiolipin and its purification yield depend upon the fatty acid composition, particularly the degree of unsaturation.

Animals↗

PubMed1994

Stretch sensitivity of transmembrane mobility of hydrogen peroxide through voids in the bilayer. Role of cardiolipin.

Availability of voids for diffusion of quinone in the membrane was shown to be the rate-limiting step in electron transport in mitochondria and chloroplasts (Mathai, J. C., Sauna, Z. E., John, O., and Sitaramam, V (1993) J. Biol. Chem. 268, 15442-15454). The primary role of voids in these diffusion-controlled reactions required a more rigorous documentation of the role of diffusion in membranes by independent measurements. The transbilayer diffusion of hydrogen peroxide as monitored by occluded catalase activity was developed as a kinetically valid probe to specifically address this question. This in turn led to unique results on the mechanistic basis of stretch (= hypo-osmotic) activation of hydrogen peroxide permeation via such voids. The rate of peroxide permeation is shown to be markedly stretch sensitive in some cells/organelles (e.g. peroxisomes) and insensitive in others (e.g. erythrocytes); this was equally true of liposomes prepared from lipids extracted from the corresponding cells/organelles. The molecular basis of stretch sensitivity was uncovered using specific binary mixtures of lipids: while pure phosphatidyl choline liposomes were stretch insensitive, these became sensitive when doped only with specific lipids, viz. cardiolipin and cerebrosides. Cholesterol abolished this stretch sensitivity in ternary mixtures. Induction of stretch sensitivity by cardiolipin was marked by lowering of activation energy for peroxide diffusion, a negative temperature coefficient for glucose permeation while further addition of cholesterol reversed these phenomena. The steady state fluorescence polarization studies revealed intimate correlations between anisotropy, hydrogen peroxide diffusion, and stretch sensitivity consistent with presence of voids in these binary mixtures.

Animals↗

PubMed1993

Mitochondrial dysfunction of a cultured Chinese hamster ovary cell mutant deficient in cardiolipin.

In our preceding paper, we reported that a temperature-sensitive Chinese hamster ovary cell mutant, PGS-S, with thermolabile phosphatidylglycerophosphate synthase was defective in the biogenesis of both phosphatidylglycerol and cardiolipin (CL) at a nonpermissive temperature (Ohtsuka, T., Nishijima, M., and Akamatsu, Y. (1993) J. Biol. Chem. 268, 22908-22913). To investigate the biological role of cardiolipin, we examined the structure and function of mitochondria in mutant PGS-S cells, since CL is primarily found in the mitochondrial membranes of eukaryotic cells. Under conditions where the formation of CL was impaired, this mutant had both morphological and functional mitochondrial abnormalities, manifested by more stringent temperature sensitivity for cell growth in glucose-deficient medium and by reduced ATP production, increased glycolysis, and reduced oxygen consumption in intact cells. Rotenone-sensitive NADH oxidase activity in cell extracts was also reduced in the mutant cultivated at a nonpermissive temperature, showing a defect(s) in the respiratory electron transport chain of mitochondria. Of the respiratory chain complexes, rotenone-sensitive NADH-ubiquinone reductase (Complex I) was most severely impaired in the mutant, whereas its activity was restored in a revertant of the mutant that had regained the ability to synthesize CL. These results suggest that CL plays a critical role in mitochondrial functions, at least in the respiratory electron transport chain.

Adenosine Triphosphate↗

PubMed1993

Fusion of chromaffin granules with cardiolipin-containing phospholipid vesicles.

Fusion of chromaffin granule ghosts with model phospholipid vesicles is dependent on the composition of the vesicle membrane. Cardiolipin was found to make possible a process of fusion in the absence of calcium. This calcium-independent fusion appears to be partially protein-dependent. Upon interaction with pure cardiolipin vesicles calcium stimulates both fusion of chromaffin granule ghosts and release of catecholamines from intact chromaffin granules. We suggest that the release of catecholamines is not only a consequence of the fusion process. The relevance of protein-lipid interaction and the importance of the formation of HII phases or other non-lamellar phases, on the fusion of chromaffin granules are discussed.

Animals↗

PubMed1998

Anti-GM1, anti-central myelin proteins, and anti-cardiolipin autoantibodies during plasma-exchange in Guillain-Barré syndrome (GBS).

We measured the autoantibodies to GM1, central myelin proteins, and cardiolipin in 30 GBS patients using sensitive ELISA and Western blot techniques. The sequential modifications of titers during plasma-exchange (PE) and at follow-up were investigated in 15 patients. In pretreatment sera, we found significantly increased antibody titers to GM1 (37% of the patients), central myelin proteins (28%), and cardiolipin (21%). Seventeen patients out of 29 (58%) presented increased IgG or IgM antibody to at least one of the antigens considered as compared to 10 out of 70 controls (14%, P = 0.00001). By Western blot, IgG or IgM antibodies reactive with the triton insoluble fraction of central myelin were observed in 19 out of 28 GBS patients (67%). The follow-up measurements during and after PE showed a declining autoantibody titer in 10 out of 15 patients. However, in the remaining 5 GBS patients, we observed a persistently elevated titer or an increase from baseline values occurring during or after PE and reaching a peak. In 2 of the 5 patients, the titer peak preceded a clinical re-exacerbation. The presence of a persistently elevated or an increasing autoantibody titer during treatment with PE merits further investigation and may help to clarify the pathogenesis of GBS and improve its treatment.

Adolescent↗