SEARCH · Search PubMed

Results for “CARDIOLIPIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,729 records · Page 96Linked to original sources

PubMed2000

Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies.

The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-beta2-glycoprotein I (beta2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to 'pure' phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific 'pure' anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein-Barr virus infection. However, anti-beta2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins.

Adolescent↗

PubMed2000

Autoantibodies to modified LDLs and other phospholipid-protein complexes as markers of cardiovascular diseases.

Recent studies have suggested that antiphospholipid antibodies contribute to the development of atherothrombosis by enhancing atherogenesis and/or by interfering with blood coagulation. The antigenic targets of antiphospholipid antibodies are cardiolipin, oxidized LDL, beta2-glycoprotein I, or prothrombin. Oxidized LDL and beta2-glycoprotein I are found in the atherosclerotic plaque and antibodies to these proteins enhance in vitro the accumulation of modified LDL into macrophages. Autoantibodies binding to modified LDL, cardiolipin and prothrombin have been associated with atherosclerosis and its thrombotic complications in sero-epidemiological studies. These autoantibodies can be used as markers of atherosclerosis but their possible pathogenic role in the athero- and thrombogenesis needs further studies.

Autoantibodies↗

PubMed2000

Mitochondrial function in ischaemia and reperfusion of the ageing heart.

1. In addition to Ca2+-dependent mediation of excitation-contraction coupling during cardiac work and ATP hydrolysis, Ca2+ also stimulates the Krebs' cycle and mitochondrial matrix dehydrogenases to maintain the nicotinamide adenine dinucleotide redox potential and ATP synthesis. Thus, the balance between energy demand and supply is maintained during increases in cardiac work by elevated cytosolic Ca2+ that is transmitted to the mitochondrial matrix via regulation of uniporter and antiporter pathways across the inner mitochondrial membrane. 2. Brief ischaemia perturbs Ca2+ homeostasis but mitochondrial buffering of Ca2+ permits maintained mitochondrial function. However, prolonged ischaemia and reperfusion causes Ca2+ 'overload' at supramicromolar levels. The onset of vicious cycles that abrogate contractile function and, ultimately, may cause irreversible cell injury involves: (i) loss of ionic homeostasis, energy production and anti-oxidant enzyme activity; (ii) activation of phospholipases; and (iii) accumulation of free radicals, membrane lipid peroxidation products and protein adducts. 3. Increased permeability of the inner mitochondrial membrane to solutes occurs causing mitochondrial swelling, 'proton leak', reduced efficiency of the respiratory chain and uncoupling of oxidative phosphorylation. The opening of the mitochondrial permeability transition pore is potentiated by high mitochondrial Ca2+ and inducers, such as Pi, long-chain acyl coenzyme (Co)A and oxygen free radicals. Opening of this channel depolarizes the mitochondrion and dissipates the H+ electrochemical gradient (delta muH), preventing oxidative phosphorylation. Together with the release of cytochrome c and subsequent activation of caspase pathways, these events precede cell death. 4. Compared with younger counterparts, the senescent myocardium has a reduced capacity to recover from ischaemia and reperfusion. The consequent events described above are augmented in ageing. Elevated mitochondrial Ca2+ and increased dehydrogenase activation are linked to inefficient mitochondrial function and limited postischaemic recovery of contractile function. 5. Notably, a distinct decrease in the ratio of mitochondrial membrane omega-3 to omega-6 polyunsaturated fatty acids (PUFA) and a decrease in the mitochondrial phospholipid cardiolipin occurs in aged rat hearts. A diet rich in omega-3 PUFA directly increases membrane omega-3:omega-6 PUFA and cardiolipin content and also facilitates improved tolerance of ischaemia and reperfusion. A major consequence of dietary omega-3 PUFA may be the effect of altered mitochondrial Ca2+ flux and Ca2+-dependent processes.

Aging↗

PubMed2006

[Congenital syphilis despite prenatal screening? An evaluation of 14 cases].

BACKGROUND: Congenital syphilis (CS) can be effectively avoided by adequate treatment of the mother during pregnancy. Nevertheless, in recent years, the Robert Koch Institute has reported 6-8 of CS cases per year. The aim of this study was to investigate cases of CS with regard to obstetrical history and results of maternal syphilis serology during pregnancy and postpartum. PATIENTS AND METHODS: Between 1997 and 2001, a total of 14 cases of CS were diagnosed after birth in the Stuttgart laboratory. Information on clinical and serological data obtained during prenatal care and at birth had been provided by the treating gynaecologists and paediatricians. Furthermore, serum samples from 11 of the 14 mothers were investigated at the Stuttgart laboratory after birth and also retrospectively at the Herford laboratory. RESULTS: All mothers presented without clinical signs of syphilis. Delayed prenatal care was observed in 6 out of 14 cases. Eleven of the 14 mothers had a positive treponemal screening test. Treatment was initiated only in two of them. During pregnancy treponemal IgM and cardiolipin antibodies were detected in none of 9 and in 5 of 8 sera of untreated mothers, respectively. In contrast, maternal serum samples investigated after birth were all positive for cardiolipin antibodies and 7 of 10 serum samples were positive for TP IgM antibodies. CONCLUSIONS: Delayed or absent prenatal care and misinterpretation of syphilis serology (or laboratory failures) in the presence of latent syphilis are mostly responsible for the inadequate management of syphilis during pregnancy and thus the occurrence of CS.

Adolescent↗

PubMed2003

Group B streptococcal phospholipid causes pulmonary hypertension.

Group B Streptococcus is the most common cause of bacterial infection in the newborn. Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung. We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention.

Animals↗

PubMed1980

Properties of an acid phosphatase in pulmonary surfactant.

Lung surfactant, a lipid-protein complex purified from dog lungs, contains a highly active phosphomonoesterase associated with it. This phosphatase is quite specific for the hydrolysis of phosphatidic acid and 1-acyl-2-lysophosphatidic acid. The enzyme possesses many of the characteristics of the microsomal enzyme, phosphatidate phosphohydrolase (EC 3.1.3.4). In addition, we have shown that this enzyme will also convert phosphatidylglycerol phosphate [1-(3-sn-phosphatidyl)-sn-glycerol-1-P] to phosphatidylglycerol [1-(3-sn-phosphatidyl)-sn-glycerol] and Pi. The phosphatidylglycerol phosphate was made available to the surfactant enzyme in a coupled assay by hydrolysis of cardiolipin [1-(3-sn-phosphatidyl)-3-(3-sn-phosphatidyl)-sn-glycerol] by stereospecific cleavage with phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) from Bacillus cereus. This enzyme has been previously shown to generate the naturally occurring isomer of phosphatidylglycerol phosphate because it has specificity for the 3-(3-sn-phosphatidyl) group of cardiolipin. Other properties of the surfactant enzyme are discussed in relation to its presence in lung surface active material.

Acid Phosphatase↗

PubMed1983

Crystallization of cytochrome bc1 complex.

Complex III (cytochrome bc1 particle; ubiquinol:ferricytochrome c oxidoreductase, EC 1.10.2.2) was purified from beef heart mitochondria by a combination of hydrophobic interaction and affinity chromatography. By washing the complex with detergent on the hydrophobic interaction column, phospholipids were effectively depleted; 7 mol of cardiolipin per mol of cytochrome c1 was retained in the final sample. NaDodSO4 gel electrophoresis showed nine polypeptide subunits in the sample. The molecular weight of the complex was estimated to be approximately equal to 225,000 from the specific heme c1 content and the subunit composition. The purified complex was crystallized by slow removal of the detergent in which the complex was dispersed. Electron micrographs and electron diffraction patterns showed that the crystal is hexagonal with unit cell dimensions a = b = 113 A, c = 132 A, and with angles alpha = beta = 90 degrees, gamma = 120 degrees. The role of bound cardiolipin in the structural integrity of the complex was discussed.

Animals↗

PubMed1997

Isolation and characterization of a structural homologue of human PRK2 from rat liver. Distinguishing substrate and lipid activator specificities.

A homologue of human protein kinase C (PKC)-related kinase-2, PRK2, which had previously escaped identification in normal mammalian tissues, was isolated from rat liver as the protease-activated kinase (PAK) originally named PAK-2. The 130-kDa cytosolic enzyme was purified to homogeneity and shown by tryptic peptide and reverse transcriptase- polymerase chain reaction (RT-PCR)-amplified rat cDNA sequence analyses to be structurally related to the 116-kDa rat hepatic PAK-1/protein kinase N (PKN) and, even more closely (95% sequence identity) to the 130-kDa human PKC-related kinase, PRK2. Rat myeloma RNA was used as the RT-PCR template because of its relative abundance in PAK-2/PRK2 mRNA compared with liver and other rat tissues. The catalytic properties of PAK-2/PRK2 in many respects resembled those of hepatic PAK-1/PKN, but were distinguished by more favorable kinetics with several peptide substrates, and greater sensitivity to PKC pseudosubstrate and polybasic amino acid inhibitors. PAK-2/PRK2 was also activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Cardiolipin activation was most evident with autophosphorylation and histone H2B phosphorylation, but only marginally evident with the favored ribosomal S6-(229-239) peptide substrate for the protease-activated kinase activity. It was concluded that PAK-2 is the rat homologue of human PRK2, with biochemical properties distinct from although overlapping those of the PAK-1/PKN/PRK1 isoform.

Amino Acid Sequence↗

PubMed1997

Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins.

We have examined the interactions of the six known rabbit neutrophil defensin antimicrobial peptides with large unilamellar vesicles (LUV) made from various lipid mixtures based on the lipid composition of Escherichia coli membranes. We find that the permeabilization of LUV made from E. coli whole lipid extracts differs dramatically from that of single-component LUV made from palmitoyl-oleoyl-phosphatidylglycerol (POPG). Specifically, defensins NP-1, NP-2, NP-3A, NP-3B, and a natural mixture of the six defensins cause fast nonpreferential leakage of high molecular weight dextrans as well as the low molecular weight fluorophore/quencher pair 8-aminonapthalene-1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide (DPX) from E. coli whole lipid LUV through large, transient membrane lesions. In contrast, release of ANTS/DPX from POPG LUV induced by the defensins is slow and graded with preference for DPX (Hristova, K., Selsted, M. E., and White, S. H. (1996) Biochemistry 35, 11888-11894). Interestingly, defensins NP-4 and NP-5 alone do not induce leakage from E. coli whole lipid LUV, whereas only NP-4 is ineffective with POPG LUV. Examination of the sequences of the six defensins suggests that the inactivity of NP-4 and NP-5 may be due to their lower net positive charge and/or the substitution of a Thr for the Arg or Lys that follows the fourth Cys residue. We found the presence of three major lipid components of E. coli whole lipid to be essential for creation of the large lesions observed in LUV: phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. Cardiolipin appears to play a key role because no leakage can be induced when only phosphatidylglycerol and phosphatidylethanolamine are present. These results indicate the importance of membrane lipid composition in the permeabilization of cell membranes by rabbit defensins.

Amino Acid Sequence↗

PubMed2003

Purification and characterization of monolysocardiolipin acyltransferase from pig liver mitochondria.

In mammalian tissues cardiolipin is rapidly remodeled by monolysocardiolipin acyltransferase subsequent to its de novo biosynthesis (Ma, B. J., Taylor, W. A, Dolinsky, V. W., and Hatch, G. M. (1999) J. Lipid Res. 40, 1837-1845). We report here the purification and characterization of a monolysocardiolipin acyltransferase activity from pig liver mitochondria. Monolysocardiolipin acyltransferase activity was purified over 1000-fold by butanol extraction, hydroxyapatite chromatography, and preparative SDS-PAGE. The purified 74-kDa protein catalyzed acylation of monolysocardiolipin to cardiolipin with [(14)C]linoleoyl coenzyme A. Photoaffinity labeling of the protein with 12-[(4-[(125)I]azidosalicyl)amino]dodecanoyl coenzyme A indicated coenzyme A was bound at its active site and photoaffinity cross-linking of 12-[(4-azidosalicyl)amino]dodecanoyl coenzyme A to the enzyme inhibited enzyme activity. Enzyme activity was optimum at pH 7.0, and the enzyme did not utilize other lysophospholipids as substrate. The purified enzyme was heat-labile and exhibited an isoelectric point of pH 5.4. To determine the enzymes kinetic mechanism the effect of varying concentrations of linoleoyl coenzyme A and monolysocardiolipin on initial velocity were determined. Double-reciprocal plots revealed parallel lines consistent with a ping pong kinetic mechanism. When the enzyme was incubated in the absence of monolysocardiolipin, coenzyme A was produced from linoleoyl coenzyme A at a rate consistent with the formation of an enzyme-linoleate intermediate. The true K(m) value for linoleoyl coenzyme A and true K(m) value for monolysocardiolipin were 100 and 44 microM, respectively. The calculated V(max) was 6802 pmol/min per mg of protein. A polyclonal antibody, raised in rabbits to the purified protein, cross-reacted with the protein in crude pig liver mitochondrial fractions. In liver mitochondria prepared from thyroxine-treated rats, the level of the protein was elevated compared with euthyroid controls indicating that expression of monolysocardiolipin acyltransferase is regulated by thyroid hormone. The study represents the first purification and characterization of a monolysocardiolipin acyltransferase activity from any organism.

Acyltransferases↗

PubMed1999

Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation and limited consensus by participants of external quality assurance programs signals a cautious approach.

Antibodies that bind phospholipid (anti-phospholipid antibodies [APA]) are a focus of major interest to both clinical and laboratory personnel across a variety of disciplines because of the assortment of disorders with which they are reportedly associated. A solid phase assay using cardiolipin as the test phospholipid (anti-cardiolipin antibody assay [ACA]) has now become a laboratory standard for the detection of APA. In the current report, data from two separate external quality assurance programs (QAP) and collected over the past four years, have been evaluated to assess the utility of the ACA. Despite attempted standardizations, exceedingly high inter-laboratory variation and a general lack of test result consensus would signal the adoption of a cautious clinical approach towards laboratory findings. For example, for a total of 21 cross-laboratory tested serum samples (tested for both IgG and IgM for 41 quantitative estimations), inter-laboratory variation for both ACA-IgG and ACA-IgM was higher than 50% in 20 of 41 testing cases (48.8%). The situation with regard to testing consensus was equally concerning. Total consensus (i.e., 100% of participating laboratories agreed that a given serum sample gave an ACA result of either negative or positive) occurred in less than 20% of cases for ACA-IgG. More importantly, in about 50% of serum testing occasions there was no general consensus in returned laboratory data (i.e., more than 80% of labs could not agree on whether a serum sample tested was either ACA-positive or ACA-negative). Thus, despite attempted international standardizations, exceedingly high inter-laboratory variation and a general lack of test result consensus would argue that the assay has limited utility. We conclude that single point laboratory results must be used with considerable caution before accepting that ACA activity is present in patient serum or not. We agree with recommendations indicating that laboratory tests should be repeated at least once prior to making a clinical diagnosis of any APS-like disorder.

Antibodies, Anticardiolipin↗

PubMed2005

Autoantibodies profile of rheumatoid arthritis patients during treatment with infliximab.

PURPOSE: Therapy with TNFa blocking agents has been associated with increased rate of anti-nuclear antibodies (ANA) and rare cases of lupus like syndromes. Our aim was to prospectively analyze a wide array of autoantibodies in rheumatoid arthritis (RA) patients before and 14 weeks after starting infliximab. MATERIAL AND METHODS: In this study, 26 consecutive active RA patients participated. All treated with infliximab at a dosage of 3 mg/kg on week 0, 2, 6 and every 8 weeks, along with weekly low dose methotrexate. Patients were evaluated at week 0 and 14. Clinical assessment included the number of tender and swollen joints, duration of morning stiffness, adverse events (AE) (including SLE-like) and ESR. Sera were collected before the 1st infusion of infliximab at week 0 and 14. The autoantibodies studied were: fluorescent ANA, anti-double-stranded-DNA (anti-ds-DNA), IgG and IgM anti-cardiolipin (ACA), anti-histone- H1 and C (H1, H2A, H2B, H3, H4), anti-SSA, -SSB, -ENA, -scleroderma 70, -thyroid peroxidase (TPO) and -neutrophilic cytoplasmatic (ANCA) antibodies. RESULTS: Of 26 patients, 17 were women. A significant decrease in duration of morning stiffness, number of tender and swollen joints and ESR were observed between week 0 and 14. During follow up (mean of 20.5+/-7.3 months), 9 patients stopped infliximab due to inefficacy or AE (most of them after the 4th infusion). Two patients developed lupus-like phenomena. ANA was found positive at baseline in 7 out of 26 patients. In 5 of them, an increase in the titer of ANA was observed at week 14. ANA negative turned positive for 8 patients. A significant increase of anti-cardiolipin (ACA)-IgM levels was observed in 8 patients and of ACA-IgG in 6, in parallel with ANA seroconversion. The mean level of anti-double-stranded-DNA (anti-ds-DNA) -IgG significantly increased from 66+/-33 to 93+/-68 IU/ml, in 4 patients to pathological levels. Four patients demonstrated an increase in anti-histone H1. Levels of ANCA, anti-ENA, -SSA, -SSB, -RNP, -scleroderma70 and -thyroid peroxidase (TPO) were negative in all patients and remained unchanged during the study. Cessation of treatment with infliximab was found to be associated with the appearance of ANA. CONCLUSION: An increased titer or a new appearance of ANA was observed in 12 out of 26 patients. The main autoantibodies found were anti-ds-DNA, ACA-IgM and -IgG and anti-histone. In our cohort, the appearance of some autoantibodies seemed to predict late cessation of treatment.

Adult↗

PubMed1982

Modifications of anionic-lipid domains preceding membrane fusion in guinea pig sperm.

The relationship between anionic-lipid concentration and the functional properties of plasma-membrane domains was explored using the guinea-pig sperm membrane as a model, with polymyxin B (PXB) as a probe. Areas of plasmalemma specialized for fusion during the acrosome reaction had a higher affinity for the probe than adjacent nonfusigenic regions. In addition, capacitation--a process preceding acrosome:plasma-membrane fusion--markedly enlarged the area susceptible to PXB binding over the acrosomal cap. Protease treatment mimicked capacitation by increasing the acrosome-reaction incidence as well as PXB binding, at enzyme concentrations not affecting the surface coat nor altering filipin/sterol localization. Both proteolytic digestion and capacitation failed to augment PXB- or filipin-affinity in nonfusigenic zones, such as the post-acrosomal segment, including its particle-free maculae. Incubation of sperm in capacitating medium supplemented with 32P-labeled phosphate, followed by lipid extraction, thin-layer chromatography, and autoradiography, revealed a radioactive band comigrating with cardiolipin and phosphatidic acid. Vermiform protrusions elicited by PXB in the outer lamellae of cardiolipin-phosphatidylcholine liposomes resembled those seen in fusional regions of sperm membrane. We conclude that (a) differing concentrations of anionic lipids are found in adjacent domains of the sperm plasma membrane; (b) these domains mirror the functional regions of the membrane, with higher anionic-lipid concentrations localized over fusional zones; (c) the surface coat does not participate in the maintenance of such domains; (d) anionic-lipid synthesis may contribute to their formation; and (e) anionic-lipid concentrations increase as the membrane becomes fusionally competent, indicating that cellular modulation of lipid domains accompanies regulation of membrane function.

Animals↗

PubMed1961

Immunologic studies of heart tissue. IV. Serologic reactions with human heart tissue as revealed by immunofluorescent methods: isoimmune, Wassermann, and autoimmune reactions.

Reactions of normal and pathologic sera with heart tissue have been investigated by the immunofluorescent method, with particular reference to presumptive autoantibodies to heart and their differentiation from blood group isoantibodies and Wassermann antibody. In the heart, blood group substances A and B were found distributed in capillary walls, vascular endothelium, and interstitial connective tissue. In surveys of randomly selected sera, isoimmune reactions against tissue blood group substances A and B were noted infrequently. This finding was considered related to the limited sensitivity of fluorescent antibody methods. Heart tissue from blood group O individuals was used for screening of pathologic sera for presence of tissue-reactive factors. Wassermann antibody was found reactive with constituents of myocardial sarcoplasm, of which the major reactant was cardiolipin. Wassermann-positive sera absorbed with beef cardiolipin gave evidence of reaction with other constituents of myofiber sarcoplasm. Sera of patients with rheumatic fever, rheumatic heart disease, rheumatoid arthritis, disseminated lupus, and liver disease frequently showed a marked reactivity with constituents of myofiber sarcoplasm. These serum factors were differentiated from Wassermann antibody. At least three patterns of immunofluorescent staining could be differentiated by the distribution of reactants in the myofiber sarcoplasm. These reactants were extractable with ethanol and methanol but not by acetone. Sera found reactive by immunofluorescence frequently gave positive flocculation and complement-fixation tests with alcohol extracts of human heart. Immunofluorescent tests were best correlated with flocculation reactions. Sarcoplasmic-reactive factors were associated in some sera with 19S gamma globulin as demonstrated by the use of fluorescent anti-19S gamma globulin. Serologic reactions with homologous or autologous heart were observed particularly frequently with sera from rheumatic patients approximately 2 weeks following cardiac surgery, as well as in some non-rheumatic patients following cardiac or thoracic surgery or acute myocardial infarction. The pathogenetic significance of these presumptive autoantibodies to heart is unknown. As yet, no definite conclusions may be drawn regarding their relationship to bound gamma globulin in rheumatic hearts or to the postcardiotomy and post-infarction syndromes.

Antibodies↗

PubMed2003

A single intravenous infusion of apoptotic cells, an alternative cell-based therapy approach facilitating hematopoietic cell engraftment, did not induce autoimmunity.

Previously, we reported that intravenous infusion of apoptotic leukocytes facilitated bone marrow (BM) engraftment across major histocompatibility barriers. This cell-based therapeutic approach is of great interest for stem cell therapy across histocompatibility barriers. Autoimmunity associated with apoptotic cell administration may, however, limit the use of this approach. Indeed, autoantigens are concentrated on the surface of apoptotic cells, and defective clearance of apoptotic bodies is associated with the occurrence of systemic autoimmune disease. In consequence, we assessed the autoimmune responses raised against ubiquitous double-stranded DNA (dsDNA) and cardiolipin autoantigens following a single intravenous infusion of apoptotic cells simultaneously to allogeneic BM administration. No difference was observed between levels of natural circulating immunoglobulin M (IgM) (anti-dsDNA and anti-cardiolipin) autoantibodies found in mice receiving allogeneic BM alone and those found in mice receiving apoptotic cells also. Pathogenic IgG autoantibody titers after apoptotic cell infusion were 9- to 200-fold lower than autoantibody titers found in lupus-prone mice and not different from titers detected in BM grafted mice. Kinetic analysis of autoantibodies after transplantation did not demonstrate any immunization against tested autoantigens after apoptotic cell infusion. Finally, neither immune complex deposition nor specific lesions were observed in the renal glomeruli of mice infused with apoptotic cells 9 months post-BM transplantation. Overall, these results show no specific toxicity of a single infusion of apoptotic cells administrated simultaneously to BM and may also shed light on factors influencing the immunogenic properties of apoptotic cells.

Animals↗

PubMed2005

Taz1, an outer mitochondrial membrane protein, affects stability and assembly of inner membrane protein complexes: implications for Barth Syndrome.

The Saccharomyces cerevisiae Taz1 protein is the orthologue of human Tafazzin, a protein that when inactive causes Barth Syndrome (BTHS), a severe inherited X-linked disease. Taz1 is a mitochondrial acyltransferase involved in the remodeling of cardiolipin. We show that Taz1 is an outer mitochondrial membrane protein exposed to the intermembrane space (IMS). Transport of Taz1 into mitochondria depends on the receptor Tom5 of the translocase of the outer membrane (TOM complex) and the small Tim proteins of the IMS, but is independent of the sorting and assembly complex (SAM). TAZ1 deletion in yeast leads to growth defects on nonfermentable carbon sources, indicative of a defect in respiration. Because cardiolipin has been proposed to stabilize supercomplexes of the respiratory chain complexes III and IV, we assess supercomplexes in taz1delta mitochondria and show that these are destabilized in taz1Delta mitochondria. This leads to a selective release of a complex IV monomer from the III2IV2 supercomplex. In addition, assembly analyses of newly imported subunits into complex IV show that incorporation of the complex IV monomer into supercomplexes is affected in taz1Delta mitochondria. We conclude that inactivation of Taz1 affects both assembly and stability of respiratory chain complexes in the inner membrane of mitochondria.

Acyltransferases↗

PubMed1994

Anticardiolipin wet workshop report. Fifth International Symposium on antiphospholipid antibodies.

An anticardiolipin wet workshop was conducted at the Fifth International Antiphospholipid Symposium (San Antonio, Texas, September 9-12, 1992). The workshop had four objectives: 1. to determine variability in measurement of immunoglobulin (Ig) G, IgM, and IgA anticardiolipin of eight unknown sera; 2. to examine the correlation between three commercial enzyme-linked immunosorbent assay (ELISA) kits and the Antiphospholipid Standardization Laboratory; 3. to examine protocols by which anticardiolipin binding to phospholipid antigens and beta 2 glycoprotein 1 (beta 2GP1) might be compared; and 4. to examine the beta 2GP1 effect on cardiolipin binding activity. Results showed good overall correlation of quantitative anticardiolipin measurements between workshop participants and the Antiphospholipid Standardization Laboratory. Correlation with individual ELISA kits was also good. With respect to the third objective, all participants showed comparable binding to cardiolipin and phosphatidylserine but none to phosphatidylcholine or beta 2GP1. Finally, beta 2GP1 enhanced, but was not essential for, anticardiolipin binding. This workshop will not settle controversies about anticardiolipin measurement and specificity, but suggests protocols to resolve these issues.

Antibodies, Anticardiolipin↗

PubMed1990

Heterogeneity of laboratory test results for antiphospholipid antibodies in patients treated with chlorpromazine and other phenothiazines.

Ninety-seven psychiatric patients who have been treated with the antipsychotic drug chlorpromazine or another phenothiazine have been investigated for the presence of antiphospholipid antibodies. A variety of coagulation studies and specific antiphospholipid immunoassays were performed to define the spectrum of antigen specificity of these antibodies. Coagulation studies showed an increasing sensitivity for the lupus anticoagulant with reagents of differing phospholipid content. Prolonged activated partial thromboplastin times (APTTs) were found in five patients with the use of an insensitive APTT reagent and in 14 patients with a lower phospholipid content reagent. In every case, attempted correction of the clotting time with normal plasma was unsuccessful. Twenty-one patients had abnormal kaolin clotting time profiles. In seven of these patients, test results with both APTT reagents had been normal. Antibody reactivity was tested against three negatively charged phospholipids, phosphatidyl-serine, cardiolipin, and phosphatidylinositol. Only five patients demonstrated reactivity against phosphatidylinositol, whereas high antibody titers were observed in 28 patients against one or both of phosphatidylserine and cardiolipin. Twenty-three of these patients were found to have elevated anticardiolipin-specific IgM antibodies. Overall, 41 of the patients had at least one laboratory abnormality suggestive of antiphospholipid antibody activity. Seven of the 26 patients, taking phenothiazines other than chlorpromazine, had positive test results for antiphospholipid antibodies. No clinical thromboembolic events were recorded in any patient. These findings demonstrate the heterogeneity of antiphospholipid antibody specificity induced in patients treated with various phenothiazine drugs and indicate that none of these patterns of reactivity marks a predisposition for thromboembolism in this population.

Adult↗