Disease relevance of Hmgb1

• We have expressed the HMG box region of the B-domain of rat HMG1 (residues 88-164 of the intact protein) in Escherichia coli and we describe here the determination of its structure by 2D 1H-NMR spectroscopy [1].
• Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages [2].
• High mobility group (HMGB)1/amphoterin is a multifunctional cytokine involved in invasion and metastasis of cancer and in inflammation [2].
• We also present a semi-quantitative estimate that HMG-1 and HMG-2 occur in chromatin from rapidly dividing, cultured rat hepatoma cells at about 8 times the level that they occur in adult rat liver chromatin [3].
• The effect of chicken erythrocyte High Mobility Group protein 1 (HMG-1) on the enzymatic hydrolysis of purified double-stranded and single-stranded bacteriophage lambda DNA was studied [3].

High impact information on Hmgb1

• The presence of HMG-1 protein in the cytoplasm of rat liver cells was verified by direct examination of the protein content of selected cytoplasmic fractions [4].
• A protein with electrophoretic mobility identical to HMG-1 was detected by electrophoresis on polyacrylamide gels containing either sodium dodecylsulfate or urea [4].
• Immunofluorescence studies with these antibodies reveal that HMG-1 or components which immunologically cross-react with HMG-1 are present in the cytoplasm of Chinese hamster V-79, rat liver TR-12 and bovine trachea EBTr-NBL-4 cells [4].
• Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion [5].
• Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin [6].

Chemical compound and disease context of Hmgb1

• The results indicate that levels of alanine aminotransferase, aspartate aminotransferase, creatinine, lactate, tumor necrosis factor, and high mobility group box 1 markedly elevated after hemorrhage and resuscitation, and AM/AMBP-1 treatment significantly attenuated these increases [7].
• High-mobility group box 1 protein is an inflammatory mediator in necrotizing enterocolitis: protective effect of the macrophage deactivator semapimod [8].
• High-mobility group 1 protein also plays an essential role in differentiation of LAN-5 neuroblastoma cells which, following stimulation with retinoic acid, express high-mobility group 1 protein on to the external surface of the plasma membrane [9].
• A 29 kD protein previously isolated from murine erythroleukemia (MEL) cells and shown to enhance the rate of differentiation of these cells has now been demonstrated to possess an amino acid sequence identical to that reported for the 30 kD heparin-binding protein from developing rat brain, named amphoterin after its highly dipolar structure [10].
• HMGB1 was found to accumulate in NMDA-treated primary cortical culture media, and supernatants collected from these cultures were found to trigger microglia activation, the hallmark of brain inflammation [11].

Biological context of Hmgb1

• 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane [12].
• Nucleotide sequence of rat liver HMG1 cDNA [13].
• Taken together, these findings indicate that thermal injury per se can markedly enhance HMG-1 gene expression in various organs [14].
• Up-regulation of HMG-1 expression may be involved in the pathogenesis of endogenous endotoxin-mediated multiple organ damage secondary to major burns [14].
• By DNA binding assays we found the HMG-1 binding sites in the rat Hp gene cis-regulatory subelements A and C and revealed an increase in its DNA-binding after induction of AP response [15].

Anatomical context of Hmgb1

• The distinct localization to the filopodia of the advancing plasma membrane suggests that endogenous amphoterin has a role in the extension of neurite-type cytoplasmic processes in developing cells [12].
• In cells that are at an active stage of spreading and extending their cytoplasmic processes amphoterin was especially associated with plasma membrane filopodia [12].
• Anti-synthetic peptide antibodies raised according to the sequence of amphoterin were shown to bind specifically to the protein isolated from brain, and were used to detect amphoterin in subcellular fractions and in immunostaining of cells [12].
• We reported recently that HMGB1 was associated with senile plaques and the total protein level significantly increased in AD brain [16].
• Testis levels of HMG proteins, relative to DNA content, were equivalent to other tissues for HMG1 (13 micrograms/mg of DNA), HMG14 (3 micrograms/mg of DNA), and HMG17 (5 micrograms/mg of DNA) [17].

Associations of Hmgb1 with chemical compounds

• In this study, diffuse HMGB1 immunoreactivity was observed around dying neurons in the kainic acid- and Abeta1-42 (Abeta42)-injected rat hippocampi [16].
• Significant losses of DNA ring closure activity were seen upon limited 2-5-h exposures of nonacid-purified HMG-1/2 to perchloric acid and/or trichloroacetic acid [18].
• HMG 1 was ADP-ribosylated to a greater extent in young but to a lower level in the old by different effectors except spermine which showed no influence in old age [19].
• Butyrate had no effect on HMG 1, but hydrocortisone decreased it [20].
• A sharp rise in the phosphorylation of histones H1, H2A, and ubiquitinated H2A is seen on transformation, together with the appearance of three phosphorylated proteins that are extractable by perchloric acid and appear related to high mobility group Protein 14, a constituent of active chromatin [21].

Physical interactions of Hmgb1

• Ligation of RAGE by amphoterin lead to rapid phosphorylation and nuclear localization of cyclic AMP response element-binding protein (CREB), a major regulator of chromogranin expression [22].
• Sp1-binding elements in the promoter of RAGE are essential for amphoterin-mediated gene expression in cultured neuroblastoma cells [23].
• Surprisingly, a deletion of 26 amino acid residues from the C-terminal extension of the androgen receptor DBD does not influence DNA binding but destroys its sensitivity to HMGB1 [24].

Regulatory relationships of Hmgb1

• HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of the rat liver haptoglobin gene [15].
• Amphoterin stimulates myogenesis and counteracts the antimyogenic factors basic fibroblast growth factor and S100B via RAGE binding [25].
• In transient transfection assays, however, HMGB1 significantly enhances the activity of the glucocorticoid and progesterone receptors but not the androgen or mineralocorticoid receptor [24].

Other interactions of Hmgb1

• The results presented in this report offered further evidence for the existence of structural and functional similarities between these two proteins implicating an involvement of HMG-1 in the regulation of the rat Hp gene transcription [15].
• Averaged over the four tissues investigated, there were 0.28 molecule of HMG1, 0.18 molecule of HMG2, and 0.46 molecule of HMG17 per nucleosome [26].
• Identification of a single-stranded DNA binding protein from rat liver with high mobility group protein 1 [27].
• This DNA-bending activity appears to be central to at least some of the recently elucidated functions of HMG-1/2, such as the enhancement of progesterone receptor DNA binding [18].
• HMG1, -2, -14, and -17 were isolated from rat testes by Bio-Rex 70 chromatography combined with preparative gel electrophoresis [17].

Analytical, diagnostic and therapeutic context of Hmgb1

• The number of PMA-U937 cells was markedly decreased by co-culture with WiDr cells exposed to HMGB1/amphoterin sense S-oligodeoxynucleotide (ODN) in spheroids or monolayers [2].
• Characterization by high performance liquid chromatography--mass spectrometry (HPLC-MS), partial peptide sequencing and western blot analysis showed the isolated HMG proteins to be HMG-1 and HMG-2 [28].
• Isoelectric focusing, HPLC-MS and peptide sequencing data also suggested that HMG-1 and SBP-1 were identical [28].
• The rat liver single-stranded DNA binding protein, S25 and HD25, isolated by differential DNA cellulose affinity chromatography was compared to the high mobility group proteins, HMG1 and HMG2, isolated from rat liver chromatin by the technique of Goodwin et al [27].
• Incorporation of [3H]lysine into the non-histone chromosomal proteins HMG1, HMG2, and HMG17 and into each of the five major classes of histones was measured in rat liver at various times after partial hepatectomy [29].

References