Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The claimed association between the M2 autoantigens of primary biliary cirrhosis (PBC) and the mitochondrial H+-ATPase has been re-examined in view of the recent reports that PBC autoantibodies react specifically with the lipoate acetyl transferases of 2-oxo acid dehydrogenases. Study of F0F1-ATPase purified from human and yeast mitochondria, and the comparison between immunoprecipitates obtained with antibodies against the H+-ATPase beta subunit and anti-M2 antibodies of PBC, established that the M2 antigens are not associated with the H+-ATPase complex. The M2 antigens did copurify with a crude bovine heart F1-ATPase preparation, but not with F1-ATPase from yeast, human heart or human liver.
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PMID:The association of the autoantigens of primary biliary cirrhosis with the mitochondrial H+-ATPase--a reassessment. 252 56

The nature of mitochondrial PBC-related antigens has been investigated with radioimmunoassay (RIA) and immunoblotting methods. The major antigen(s) was located by RIA in beef heart mitochondria, submitochondrial particles, chloroform-extracted F1-ATPase and Complex III. Cross-competition RIA experiments showed that the same antigen is present in all the above samples but at different concentrations. The antigen is not present in purified F1-ATPase, cytochrome oxidase, the oligomycin sensitivity conferring protein (OSCP), Factor6, or the Transhydrogenase. Immunoblot analysis of the above mitochondrial proteins revealed two PBC-related antigens (apparent molecular weights of 70 KD and 60 KD) whose distribution in the various proteins and protein complexes correlated well with the antigens determined by RIA. Immunoblot analysis of mitochondrial antigens was carried out using sera from normal subjects and from patients with PBC and with different autoimmune diseases (AID). Only PBC sera reacted with the 70 KD and 60 KD antigens. The PBC antigen detected by RIA in submitochondrial particles and the chloroform-F1-ATPase could be blocked by Mersalyl, suggesting its relationship to the mitochondrial 'M2' antigen. Furthermore, the antigenicity of the 70 KD peptide was shown by immunoblotting to be dependent upon mercaptoethanol. Thus, not only is the antigenicity of the 70 KD component dependent on a sulphur group, but the sulphur must be in the reduced form.
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PMID:Primary biliary cirrhosis: further biochemical and immunological characterization of mitochondrial antigens. 286 43

Sera with anti-mitochondrial autoantibodies detected by indirect immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA) were examined by immunoblotting against pig heart mitochondria. Seven types of reactions were defined, according to the pattern of the labelled bands. Type I sera reacted with 12 bands located within four zones. The most intensively labelled bands were located at 70, 67, 58, 63 and 43 kDa. Other types gave decreasing band numbers. When beef heart mitochondria were used, sera belonging to each of the above types had a profile of labelled bands which sometimes differed from those obtained with pig heart mitochondria. When the chloroform extracted F1-ATPase from beef heart mitochondria was used to prepare the immunoblots, primary biliary cirrhosis (PBC) sera with anti-mitochondria antibodies reacted with all the bands although zone A bands were less labelled. Rat liver mitochondria gave seven bands with type I sera among which the 57 and 35 kDa bands were specific for rat liver mitochondria, as shown by absorption tests. Sera of PBC patients were also tested in immunoblotting against rat liver subcellular fractions including mitoplasts, submitochondrial particles, inner membrane, outer membrane, matrix proteins and inter-membrane proteins. Antigenic bands of A and B zones were localized in the inner membrane and/or in the matrix proteins and the 35 kDa band in inter-membrane proteins. The outer membrane gave no reaction. The most frequent anti-mitochondrial autoantibody types in PBC were type II, then I, whilst for chronic active hepatitis type III was the most common. Type V was only seen in a patient suffering from a typical PBC. Some sera from patients with syphilis, collagenous colitis or progressive systemic sclerosis labelled one or two bands distinct from those labelled by the PBC sera. Sera from patients with drug-induced hepatitis with endoplasmic reticulum antibodies and with systemic lupus erythematosus were generally found negative by immunoblotting.
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PMID:Use of immunoblotting to characterize the mitochondrial antigens recognized by anti-mitochondrial autoantibodies. 317 Nov 87

The antigenic reactivities of circulating IgM- and IgG-type antimitochondrial antibodies (AMA) from 18 patients with primary biliary cirrhosis (PBC) were compared by the use of immunoblotting and enzyme-linked immunosorbent assay (ELISA). In immunoblotting, the binding patterns of IgM and IgG were very similar when F1-ATPase and mitochondria were used as antigens. The major PBC-specific IgM-reactive antigen was identical with the dominating IgG-reactive antigen, sharing the same molecular weight of 70 kD and the same requirement for reduced thiol groups for expression of antigenicity. Other PBC-related mitochondrial proteins with variable antigenicity had the molecular weights of 60 and 43 kD. Depending on the IgM and IgG reactions in F1-ELISA, PBC patients can be grouped into three categories: patients with IgG and IgM (12/18), IgG alone (5/18) and IgM alone (1/18). By serum fractionation, the IgM reactivity was shown to be a true PBC-related antibody antigen reaction, and not due to interference of rheumatoid factors.
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PMID:Primary biliary cirrhosis: antigenic specificity of IgM-type mitochondrial antibodies analyzed by immunoblotting and ELISA. 329 73

Peripheral blood mononuclear cells from 7 patients with primary biliary cirrhosis and 7 healthy control subjects were studied for their ability to produce antibodies to mitochondrial antigens in vitro. Peripheral blood mononuclear cells were collected by lymphapheresis and cultured with or without pokeweed mitogen for 10 days. The culture supernatants were then tested for antibodies to mitochondrial antigens by both immunofluorescence microscopy and a microtiter ELISA. Peripheral blood mononuclear cells from 5 of 7 patients with primary biliary cirrhosis but from none of the healthy controls produced antibodies to mitochondrial antigens spontaneously (without pokeweed mitogen stimulation). In contrast, peripheral blood mononuclear cells from 6 of 7 patients with primary biliary cirrhosis and from 6 of 7 control subjects synthesized detectable levels of antibodies to mitochondrial antigens after stimulation with pokeweed mitogen. In general, peripheral blood mononuclear cells from the primary biliary cirrhosis patients produced higher titers of antibodies to mitochondrial antigens in culture than cells from healthy controls. Furthermore, the antibodies to mitochondrial antigens reactivity produced by peripheral blood mononuclear cells of primary biliary cirrhosis patients exhibited a specificity for the M2 mitochondrial antigen which is present on the inner membrane of mitochondrial cristae and which is closely associated with a mitochondrial ATPase activity. In contrast, the antibodies to mitochondrial antigens reactivity produced by peripheral blood mononuclear cells of healthy controls appeared to be directed at a broader range of mitochondrial antigens. These findings indicate that, inpatients with primary biliary cirrhosis, there is a marked expansion of B lymphocyte clones that produce an antibody to a specific mitochondrial antigen.
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PMID:The in vitro production of antibodies to mitochondrial antigens by peripheral blood mononuclear cells from patients with primary biliary cirrhosis. 375 49

The complement fixing antigen of the inner mitochondrial membrane previously shown to be associated with the mitochondrial ATPase could be further purified by subjecting the ATPase extracted from beef heart and brown fat mitochondria to ion exchange and gel filtration chromatography. Although the ATPase activity could be clearly dissociated from the complement fixing activity, subunits of the F1-ATPase complex were always found in the purified fractions. The alpha, gamma, delta and epsilon subunits of the complex could be excluded with high probability as target antigens in contrast to the beta band which was always found in association with the antigen activity. These findings imply that the active centre of the ATPase enzyme is not involved in the antibody reaction but molecules of the ATPase complex may have antigen binding capacity. Treatment of ATPase associated antigen with trypsin did not markedly affect the complement binding, while SMP's treated in the same way lost their antigen activity indicating that sera from patients with primary biliary cirrhosis (PBC) may have mitochondrial antibodies of different specificities reacting with trypsin sensitive as well as trypsin insensitive components of the inner membrane. The purified antigen reacted exclusively with sera from patients with PBC and may be therefore used as a marker antigen.
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PMID:Mitochondrial antibodies in primary biliary cirrhosis. VI. Association of the complement fixing antigen with a component of the mitochondrial F1-ATPase complex. 618 57

The amounts of an antigen to primary biliary cirrhosis (PBC) which occur in subcellular fractions of Trypanosoma rhodesiense and T. lewisi correlate positively with the oligomycin-sensitive (OS) ATPase activity of these fractions. This result is consistent with the mitochondrial ATPase association of the antigen in mammalian and other cells. Higher levels of OS-ATPase and of PBC antigen in T. lewisi accord with a more extensive mitochondrial development in this species.
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PMID:Correlation of oligomycin-sensitive ATPase activity in trypanosomes with their content of an antigen to primary biliary cirrhosis. 623 98

Antigens to primary biliary cirrhosis (PBC) appeared to be identical in wild type (rho+) and petite (rho o) mutant S.cerevisiae. As the latter mutants lack functional mitochondria, the PBC antigens, which are associated with mitochondrial ATPase in other cells, may be of nucleocytoplasmic origin.
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PMID:Detection of an antigen to primary biliary cirrhosis in wild type and petite mutant Saccharomyces cerevisiae. 639 93

Antimitochondrial antibodies are found in a variety of autoimmune liver diseases, particularly primary biliary cirrhosis. The antigen against which these antibodies are directed is localized on the inner mitochondrial membrane. Earlier work suggested that this antigen was associated with the mitochondrial ATPase. However, we have succeeded in separating the enzyme activity from the antigenic activity using gel filtration and ion-exchange chromatography. Furthermore, the antigenic activity is not affected by modulators of ATPase enzymatic activity like aurovertin or oligomycin. The antigenic activity is, however, very susceptible to reagents which block thiol groups. The mitochondrial antigen, in contrast to the ATPase enzyme, is found in high amounts in brown fat mitochondria. Identification of this antigen may help to explain why specific antimitochondrial antibodies arise in the sera of patients with primary biliary cirrhosis.
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PMID:Antimitochondrial antibodies (AMA) in primary biliary cirrhosis. I. Separation of the PBC antigen activity from mitochondrial ATPase activity. 646 Jul 55