Disease relevance of ADAM8

• Tumor tissue microarray was applied to examine expression of ADAM8 protein in archival lung cancer samples from 363 patients [1].
• A high level of ADAM8 expression was significantly more common in advanced-stage IIIB/IV adenocarcinomas than in adenocarcinomas at stages I-IIIA [1].
• A soluble ADAM8 protease containing a pro- and metalloprotease domain was expressed in E. coli and purified as active protease owing to autocatalytic prodomain removal [2].
• In brain tumor tissue, ADAM8 and ADAM19 undergo activation by prodomain removal resulting in active proteases [3].
• This is compatible with a role for ADAM8 in the formation of foreign body giant cells and osteoclasts [4].
• SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells [5].

Psychiatry related information on ADAM8

• Sorption of MS2 bacteriophage to layered double hydroxides: effects of reaction time, pH, and competing anions [6].

High impact information on ADAM8

• Binding of mammalian ribosomes to MS2 phage RNA reveals an overlapping gene encoding a lysis function [7].
• Among amino acid codons that require a third-position pyrimidine, there is a significant bias favoring the use of cytidine over uracil in MS2 phage RNA [8].
• Hybrid proteins containing RS domains fused to the MS2 RNA binding protein were tested in vitro with RNA substrates bearing an MS2 recognition sequence [9].
• The thermodynamic contribution of a stacking interaction between Tyr85 in MS2 coat protein and a single-stranded pyrimidine in its RNA binding site has been examined [10].
• Mutagenesis of a stacking contact in the MS2 coat protein-RNA complex [10].

Chemical compound and disease context of ADAM8

• Sequence of the A-protein of coliphage MS2. I. Isolation of A-protein, determination of the NH2- and COOH-terminal sequences, isolation and amino acid sequence of the tryptic peptides [11].
• Sequence of the A-protein of coliphage MS2. III. Isolation and sequence determination of thermolytic peptides and soluble cyanogen bromide fragments: alignment of 363 amino acid residues of a total of 393 [12].
• One proline residue, Pro78, is strictly conserved in the coat protein of all related bacteriophages, and in the case of MS2 this proline residue is preceded by a cis peptide bond in the B subunit [13].
• By the addition of Tween 80 to suspensions of MS2 and R17, phage inactivation was prevented [14].
• Filters containing diatomaceous earth modified by in situ precipitation of a combination of ferric chloride and aluminum chloride adsorbed greater than 80% of enteroviruses (poliovirus 1, echovirus 5, and coxsackievirus B5) and coliphage MS2 present in tap water at ambient pH (7.8 to 8.3), even after filtration of 100 liters of tap water [15].

Biological context of ADAM8

• Up-regulation of ADAM8 expression on dendritic cells was also observed after stimulation with TNF-alpha, but not after stimulation with anti-CD40 [16].
• CD156 (human ADAM8): expression, primary amino acid sequence, and gene location [17].
• Additionally, ADAM8 mRNA expression was quantified by real-time reverse transcription polymerase chain reaction (n = 59) [18].
• ADAM-8 expression was negatively correlated with the forced expiratory volume at the first second (FEV(1)) (r = -0.57, P < 0.01), whereas ADAMTS-1 and RECK expressions were positively correlated to FEV(1) (r = 0.45, P < 0.05, and r = 0.55, P = 0.01, respectively) [19].
• An earlier expression study using partial MS2 cDNA clones had indicated that the stability of this hairpin is important for gene expression [20].

Anatomical context of ADAM8

• The ADAM8-dependent release of sCD23 and the endogenous release from B cell lines could be similarly inhibited by a hydroxamic acid, metalloprotease inhibitor compound [21].
• Here we demonstrate for the first time ADAM8 protein expression on B cells and dendritic cells, and its higher expression on CD14(2+)CD16(-) monocytes compared to CD14(+)CD16(+) cells [16].
• ADAM8 mRNA and protein are found at low levels throughout the normal mouse CNS, in neurons and oligodendrocytes [22].
• In the WR CNS regions in which neurodegeneration occurs, ADAM8 is induced in neurons, reactive astrocytes, and activated microglia [22].
• RT-PCR using ADAM-specific primers enabled us to identify the expression of ADAM 8, 9, 10, 15, 17, and 28 in both osteoclasts and osteoblasts [23].

Associations of ADAM8 with chemical compounds

• Materials and Methods: Chinese hamster ovary cells (CHO) expressing different integrin subunits were tested for their capacity to bind the disintegrin domain of ADAM8 [24].
• Addition of antisense (AS) S-oligonucleotides for ADAM8 (1-10 nM) to mouse bone marrow cultures treated with 10(-9) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibited OCL formation compared with treatment with the control S-oligonucleotide [25].
• Electron microscopy studies revealed that MS2 affinity-selected B complexes exhibit a rhombic shape with a maximum dimension of 420 A and are structurally more homogeneous than B complexes treated with heparin [26].
• Two adducts (MS1 and MS2) bound to the immobilized boronate column indicating the presence of cis-vicinal hydroxyl groups, a configuration which would result from reaction of 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydroBaP (anti-BaPDE) with DNA [27].
• Chain elongation studies utilizing an MS2 RNA template showed that (-)-carbovir 5'-triphosphate terminated transcription at positions identical to those where dideoxy-GTP terminated [28].

Enzymatic interactions of ADAM8

• In this report we demonstrate that soluble ADAM8 is an active metalloprotease in vitro and is able to hydrolyse myelin basic protein and a variety of peptide substrates based on the cleavage sites of membrane-bound cytokines, growth factors and receptors which are known to be processed by metalloproteinases [29].

Regulatory relationships of ADAM8

• The in vivo relevance of the ProteaseSpot method was confirmed by cleavage of full-length APP with ADAM8 in human embryonic kidney 293 cells expressing tagged APP [2].

Other interactions of ADAM8

• The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs [29].
• The lack of TIMP inhibition of ADAM8 and 9 contrasts with other membrane-associated metalloproteinases characterised to date in this respect (ADAM10, 12, 17, and the membrane-type metalloproteinases) which have been implicated in protein processing at the cell surface [29].
• We conclude that ADAM8 could contribute to ectodomain shedding of CD23 and may thus be a potential target for therapeutic intervention in allergy and inflammation [21].
• From 34 peptides tested in the peptide cleavage assay, significant cleavage by soluble ADAM8 was observed for 14 peptides representing membrane proteins with functions in inflammation and neurodegeneration, among them the beta-amyloid precursor protein (APP) [2].
• The proportion of the serum ADAM8-positive cases defined by our criteria was 63% and that for carcinoembryonic antigen was 57%, indicating equivalent diagnostic power of these two markers [1].

Analytical, diagnostic and therapeutic context of ADAM8

• Serum ADAM8 levels of 105 lung cancer patients and 72 controls were also measured by ELISA [1].
• Western blot analysis confirmed that the soluble form of ADAM8 is present in normal marrow cultures [25].
• RESULTS: In situ hybridization disclosed ADAM8 mRNA in mono- and multinuclear cells in both interface and control synovial samples [4].
• Increased expression of a novel osteoclast-stimulating factor, ADAM8, in interface tissue around loosened hip prostheses [4].
• Analysis of BaP:deoxyribonucleoside adducts resolved by immobilized boronate chromatography and reversephase high-performance liquid chromatography demonstrated the presence of three BaP:deoxyribonucleoside adducts in both cells: M2, MS1, and MS2 in a ratio of 1.6:1:14 [27].

References