Disease relevance of Dlat

• Mitochondrial autoantibodies are characteristic of the disease primary biliary cirrhosis (PBC), but the immunoreactive mitochondrial antigens have not been defined [1].
• In these respects, E2 is similar to the bacteriophage lambda repressor, which can act either as a repressor or an activator of transcription depending on the position of its binding sites relative to the promoter sequences [2].
• In contrast, the same full-length E2 protein repressed transcription of the HPV-18 E6/E7 P105 promoter [2].
• We recently reported the development of PBC-like lesions in SJL mice sensitized with PDC and have named this model disease experimental autoimmune cholangitis (EAC) [3].
• The autoimmune liver disease primary biliary cirrhosis (PBC) is characterized by autoreactive responses to a highly conserved self-antigen, pyruvate dehydrogenase complex (PDC) [3].

Psychiatry related information on Dlat

• Morris water maze results showed that ovarian steroid deprivation resulted in spatial memory impairment, while melatonin and E2 significantly ameliorated spatial memory deficits in OVX rats [4].
• These findings demonstrate the important effects of melatonin and E2 on cholinergic neurons and support the potential application of melatonin in the treatment of dementia in postmenopausal women [4].
• In Wistar Kyoto (WKY) strain, being the normotensive controls, E2 in doses of 8 and 16 mcg decrease in blood pressure was less pronounced and amounted 1.200 and 1.467 kPa, respectively, whereas the pain threshold increased by 7.2 and 10.4 (g x 10), respectively [5].

High impact information on Dlat

• The products encoded by the E2 open reading frame of the papillomaviruses are DNA-binding transcription factors involved in the positive or negative regulation of multiple viral promoters [2].
• We have identified autoantibodies from two patients with primary biliary cirrhosis (PBC) that recognize the nuclear envelope of mammalian cells on indirect immunofluorescence microscopy [6].
• These findings, along with the previous discovery of autoantibodies against an integral membrane glycoprotein (gp210) of the nuclear pore membrane in patients with PBC, suggest that antibodies against integral membrane proteins of the nuclear envelope are characteristic of a subset of patients with PBC [6].
• Transient expression assays demonstrated that elements in regions E1 and E3, but not necessarily E2, are required for full enhancer activity [7].
• This study investigated the changes in circulating thioredoxin and nitrosothiols and the relationship with protein sulfhydryls (PSH), hepatic concentrations, hyaluronate, and histology in patients with primary biliary cirrhosis (PBC) and in rats with bile duct ligation (BDL) [8].

Chemical compound and disease context of Dlat

• Antibody to two forms of dihydrolipoamide acetyltransferase (PDC-E2) in primary biliary cirrhosis [9].
• Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex [10].
• BCKAD E1alpha subunit mRNA in muscle of acidotic rats given dexamethasone was increased 1.89-fold (P < 0.05) in parallel with the change in BCKAD activity; BCKAD E2 subunit mRNA was increased by acidosis, dexamethasone, or a combination of both stimuli [11].
• Reduced renal 15-hydroxyprostaglandin dehydrogenase (PGDH) activity has been proposed as a cause, subsequent to elevation of intrarenal prostaglandin (PG) E2 levels, of the development or maintenance of high blood pressure (BP) in the New Zealand genetically hypertensive (NZGH) rat [12].
• In adulthood, feminine sexual behavior (lordosis) was tested after E2 plus progesterone priming [13].

Biological context of Dlat

• We used a rat liver cDNA library in lambda gt 11-Amp3 to clone a 1370-base pair insert that coded for a polypeptide reactive with PBC sera [1].
• These E2 components possess the sequence G-X-G-X-X-G, which is the consensus sequence for nucleotide binding sites of nucleotide binding proteins, in the E3 and/or E1 binding domains [14].
• The amino acid sequence of a full mature protein of rat PDC-E2 was predicted by combination of the cDNA nucleotide sequence and the N-terminal amino acid sequence determined chemically [14].
• Despite the likelihood of extensive sequence homology with mouse PDC (there is a greater than 95% sequence identity between rat and human PDC-E2 subunits), bPDC was highly immunogenic inducing significant T- and B-cell responses in the absence of any form of adjuvant [3].
• The binding affinity of E1 to the E2 core was not affected by mutation of the phosphorylation sites to glutamates, suggesting no gross perturbation of the association of E1 with the E2 core [15].

Anatomical context of Dlat

• By immunoblotting with sera from patients with primary biliary cirrhosis, we observed a double band, of molecular weight 70 and 74 kD for PDC-E2, when a preparation of bovine heart mitochondria was not boiled prior to electrophoresis [9].
• Nuclear extracts derived from C2 myotubes protected three regions (designated E1, E2, and E3) on this fragment from digestion, which indicated there may be three or more trans-acting factors that interact with the creatine kinase muscle enhancer [7].
• PSH in erythrocytes were significantly decreased in stage III and IV PBC and at day 10 after BDL [8].
• Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are presumed autoimmune chronic cholestatic liver diseases characterized by cholangitis and progressive loss of bile ducts [16].
• P1-initiated transcripts contained RNA species both with and without exon 2 (E2) sequences, except in the pancreas, adrenal, and stomach, where E2-containing sequences predominated [17].

Associations of Dlat with chemical compounds

• A complementary DNA (cDNA) clone of dihydrolipoamide acetyltransferase (E2) of the rat pyruvate dehydrogenase complex (PDC) was isolated from a lambda gt11 rat heart cDNA library [14].
• This double band could also be detected using antisera raised in rats or rabbits against intact PDC or PDC-E2, but not in antisera raised against a synthetic decamer representing the lipoic acid binding sequence of PDC-E2; the latter reacted only with the 74 kD component [9].
• Rat liver and kidney homogenates, fortified with the appropriate cofactors, produced H2O2 when incubated with prostaglandin (PG) E2 or its CoA ester (PGE2-CoA), indicating that PGE2-CoA served as substrate for acyl-CoA oxidase, the first enzyme of peroxisomal beta-oxidation [18].
• Kinetic evidence for direct transfer of alpha-ketoglutarate and NADH, within these complexes, has been obtained by measuring steady-state rates of E2 when most of the substrate or coenzyme is bound to the aminotransferase or glutamate dehydrogenase (E1) [19].
• The additional 50 000-Mr polypeptide, previously found to be associated with the pyruvate dehydrogenase complex, was apparently not a proteolytic fragment of E2 or E3, since it could be detected as a normal component in boiled sodium dodecyl sulphate extracts of whole cells [20].

Analytical, diagnostic and therapeutic context of Dlat

• Thus, according to whether preparations of PDC are boiled or not, two conformationally alternative forms of the PDC-E2 protein can be revealed by immunoblotting [9].
• By ELISA, sera from patients with primary biliary cirrhosis reacted more strongly with a non-boiled than a boiled PDC-E2, whereas immune animal sera reacted equally with both preparations [9].
• Gel retardation assays revealed that factors able to bind specifically to E1, E2, and E3 are present in a wide variety of tissues and cell types [7].
• Incubation of human or pig PDC with Q(0) followed by matrix-assisted laser desorption ionization time-of-flight and liquid chromatography/electrospray ionization mass spectrometry analyses of chymotrypsin-digested peptides of PDC E2 confirmed that Q(0) bonds to the dihydrolipoamide in these proteins [21].
• The presence of prostaglandins D2, E2, and F2 alpha was demonstrated and their contents measured in various regions of postmortem human brain, pineal body, and pituitary by using specific radioimmunoassays and gas chromatography-mass spectrometry [22].

References