Did you mean: beta microglobulin
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Atherosclerosis Mar 2021Beta-2-microglobulin (B2M) has been suggested as an emerging biomarker for cardiovascular diseases (CVD), including coronary heart disease (CHD) and stroke, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Beta-2-microglobulin (B2M) has been suggested as an emerging biomarker for cardiovascular diseases (CVD), including coronary heart disease (CHD) and stroke, and mortality.
METHODS
Three databases were searched from inception to January 2, 2020, supplemented by scanning reference lists of identified studies. We identified studies that reported associations of baseline serum or plasma B2M and CVD incidence, CVD mortality, or CHD and stroke separately, in either general populations or patients with renal disease. Relative risks (RR) were extracted and harmonized to a comparison of the highest versus lowest third of the distribution of B2M, and the results were aggregated.
RESULTS
Sixteen studies (5 in general populations, and 11 in renal disease populations) were included, involving 30,988 participants and 5391 CVD events. Based on random-effects meta-analysis, the pooled adjusted RRs comparing the highest versus lowest third of the distribution of B2M were 1.71 (95%CI: 1.37-2.13) for CVD, 2.29 (1.51-3.49) for CVD mortality, 1.64 (1.14-2.34) for CHD, and 1.51 (1.28-1.78) for stroke, with little to high heterogeneity between studies (0.0% ≤ I ≤ 80.0%). The positive associations between B2M and risks of CVD outcomes remained broadly significant across subgroup analyses. Moreover, the pooled adjusted RRs were 2.51 (1.94-3.26; I = 83.7%) for all-cause mortality and 2.64 (1.34-5.23; I = 83.1%) for infectious mortality.
CONCLUSIONS
Available observational data show that there are moderate positive associations between B2M levels and CVD events and mortality, although few studies have been conducted in general populations.
Topics: Cardiovascular Diseases; Coronary Disease; Dietary Supplements; Humans; Stroke; beta 2-Microglobulin
PubMed: 33581388
DOI: 10.1016/j.atherosclerosis.2021.01.018 -
Chinese Medical Journal Feb 2016This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate. (Review)
Review
OBJECTIVE
This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate.
DATA SOURCES
The data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search.
STUDY SELECTIONS
Articles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules.
RESULTS
β2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis.
CONCLUSIONS
Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.
Topics: Antigens, CD1; Hemochromatosis Protein; Histocompatibility Antigens Class I; Humans; Receptors, Fc; beta 2-Microglobulin
PubMed: 26879019
DOI: 10.4103/0366-6999.176084 -
Journal of Dairy Science Feb 1982beta 2-Microglobulin has been isolated from several species, but only bovine beta 2-microglobulin, previously known as lactollin, has been crystallized. An improved... (Comparative Study)
Comparative Study Review
beta 2-Microglobulin has been isolated from several species, but only bovine beta 2-microglobulin, previously known as lactollin, has been crystallized. An improved method for its isolation from colostrum is described. The bovine homologue exhibits a concentration-dependent aggregation behavior. beta 2-Microglobulin is related to both immune and histocompatibility antigen systems. It exhibits homology with the constant domains of the immunoglobulin-G light and heavy chains and is an integral part of histocompatibility antigens bound to cell surface. beta 2-Microglobulin also occurs in the free state in various body fluids including milk and colostrum. The possible relationship of elevated free beta 2-microglobulin of pathological conditions is suggested for future research.
Topics: Amino Acid Sequence; Animals; Beta-Globulins; Cattle; Colostrum; HLA Antigens; Histocompatibility Antigens; Humans; Milk; beta 2-Microglobulin
PubMed: 6176605
DOI: 10.3168/jds.S0022-0302(82)82193-0 -
Journal of the American Society For... Jul 2021NMR studies and X-ray crystallography have shown that the structures of the 99-residue amyloidogenic protein β-microglobulin (βm) and its more aggregation-prone...
NMR studies and X-ray crystallography have shown that the structures of the 99-residue amyloidogenic protein β-microglobulin (βm) and its more aggregation-prone variant, D76N, are indistinguishable, and hence, the reason for the striking difference in their aggregation propensities remains elusive. Here, we have employed two protein footprinting methods, hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP), in conjunction with ion mobility-mass spectrometry, to probe the differences in conformational dynamics of the two proteins. Using HDX-MS, a clear difference in HDX protection is observed between these two proteins in the E-F loop (residues 70-77) which contains the D76N substitution, with a significantly higher deuterium uptake being observed in the variant protein. Conversely, following FPOP-MS only minimal differences in the level of oxidation between the two proteins are observed in the E-F loop region, suggesting only modest side-chain movements in that area. Together the HDX-MS and FPOP-MS data suggest that a tangible perturbation to the hydrogen-bonding network in the E-F loop has taken place in the D76N variant and furthermore illustrate the benefit of using multiple complementary footprinting methods to address subtle, but possibly biologically important, differences between highly similar proteins.
Topics: Amino Acid Substitution; Humans; Hydrogen Deuterium Exchange-Mass Spectrometry; Protein Conformation; Protein Footprinting; beta 2-Microglobulin
PubMed: 33586970
DOI: 10.1021/jasms.0c00438 -
Cancer Biology & Therapy 2019Beta 2-microglobulin (βm) is a component of the major histocompatibility complex (MHC) class I molecule, which presents tumor antigens to T lymphocytes to trigger...
Beta 2-microglobulin (βm) is a component of the major histocompatibility complex (MHC) class I molecule, which presents tumor antigens to T lymphocytes to trigger cancer cell destruction. Notably, βm has been reported as persistently expressed, rather than down regulated, in some tumor types. For renal cell and oral squamous cell carcinomas, βm expression has been linked to increased migratory capabilities. The migratory ability of pancreatic cancer cells contributes to their metastatic tendencies and lethal nature. Therefore, in this study, we examined the impact of βm on pancreatic cancer cell migration. We found that βm protein is amply expressed in several human pancreatic cancer cell lines (S2-013, PANC-1, and MIA PaCa-2). Reducing βm expression by short interfering RNA (siRNA) transfection significantly slowed the migration of the PANC-1 and S2-013 cancer cell lines, but increased the migration of the MIA PaCa-2 cell line. The amyloid precursor-like protein 2 (APLP2) has been documented as contributing to pancreatic cancer cell migration, invasiveness, and metastasis. We have previously shown that βm/HLA class I/peptide complexes associate with APLP2 in S2-013 cells, and in this study we also detected their association in PANC-1 cells but not MIA PaCa-2 cells. In addition, siRNA down regulation of βm expression diminished the expression of APLP2 in S2-013 and PANC-1 but heightened the level of APLP2 in MIA PaCa-2 cells, consistent with our migration data and co-immunoprecipitation data. Thus, our findings indicate that βm regulates pancreatic cancer cell migration, and furthermore suggest that APLP2 is an intermediary in this process.
Topics: Amyloid beta-Protein Precursor; Cell Line, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Histocompatibility Antigens Class I; Humans; Nerve Tissue Proteins; Pancreatic Neoplasms; beta 2-Microglobulin
PubMed: 30810435
DOI: 10.1080/15384047.2019.1580414 -
The Journal of Biological Chemistry Dec 2022Self-association of WT βmicroglobulin (WT-βm) into amyloid fibrils is associated with the disorder dialysis related amyloidosis. In the familial variant D76N-βm, the...
Self-association of WT βmicroglobulin (WT-βm) into amyloid fibrils is associated with the disorder dialysis related amyloidosis. In the familial variant D76N-βm, the single amino acid substitution enhances the aggregation propensity of the protein dramatically and gives rise to a disorder that is independent of renal dysfunction. Numerous biophysical and structural studies on WT- and D76N-βm have been performed in order to better understand the structure and dynamics of the native proteins and their different potentials to aggregate into amyloid. However, the structural properties of transient D76N-βm oligomers and their role(s) in assembly remained uncharted. Here, we have utilized NMR methods, combined with photo-induced crosslinking, to detect, trap, and structurally characterize transient dimers of D76N-βm. We show that the crosslinked D76N-βm dimers have different structures from those previously characterized for the on-pathway dimers of ΔN6-βm and are unable to assemble into amyloid. Instead, the crosslinked D76N-βm dimers are potent inhibitors of amyloid formation, preventing primary nucleation and elongation/secondary nucleation when added in substoichiometric amounts with D76N-βm monomers. The results highlight the specificity of early protein-protein interactions in amyloid formation and show how mapping these interfaces can inform new strategies to inhibit amyloid assembly.
Topics: Humans; beta 2-Microglobulin; Amyloid; Amyloidogenic Proteins; Amino Acid Substitution; Amyloidosis; Biophysical Phenomena; Polymers
PubMed: 36328246
DOI: 10.1016/j.jbc.2022.102659 -
Biomolecules Jul 2023Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the...
Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the plasma, followed by renal excretion. In patients with impaired renal function, B2M will accumulate in organs and tissues leading to significantly reduced life expectancy and quality of life. While current hemodialysis methods have been successful in managing electrolyte as well as small and large molecule disturbances arising in chronic renal failure, they have shown only modest success in managing plasma levels of B2M and similar sized proteins, while sparing important proteins such as albumin. We describe a systematic protein design effort aimed at adding the ability to selectively remove specific, undesired waste proteins such as B2M from the plasma of chronic renal failure patients. A novel nanoparticle built using a tetrahedral protein assembly as a scaffold that presents 12 copies of a B2M-binding nanobody is described. The designed nanoparticle binds specifically to B2M through protein-protein interactions with nanomolar binding affinity (~4.2 nM). Notably, binding to the nanoparticle increases the effective size of B2M by over 50-fold, offering a potential selective avenue for separation based on size. We present data to support the potential utility of such a nanoparticle for removing B2M from plasma by either size-based filtration or by polyvalent binding to a stationary matrix under blood flow conditions. Such applications could address current shortcomings in the management of problematic mid-sized proteins in chronic renal failure patients.
Topics: Humans; Kidney Failure, Chronic; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; beta 2-Microglobulin; Nanoparticles
PubMed: 37509158
DOI: 10.3390/biom13071122 -
Annals of the Rheumatic Diseases Apr 1984Repeated determinations of beta 2-microglobulin (beta 2m) and beta 2-microglobulin binding activity (beta 2m ba) in serum were performed during a follow-up of 23...
Repeated determinations of beta 2-microglobulin (beta 2m) and beta 2-microglobulin binding activity (beta 2m ba) in serum were performed during a follow-up of 23 patients with SLE. beta 2m was determined by a radioimmunoassay. Individual mean values were raised in 65% of the patients. The mean value for all patients, 2.9 mg/l, was significantly higher than that of the controls. The beta 2m concentrations parallelled the clinical disease activity in several cases with different disease manifestations. The beta 2m ba was determined by precipitation of 125I-labelled beta 2m with polyethylene glycol. Increased beta 2m ba was found in 26% of the SLE patients with the 90th percentile in 40 healthy subjects being taken as the upper normal limit. There were, however, no significant differences between the mean values for beta 2m ba in the patients and the controls. Patients with systemic lupus erythematosus (SLE), suffering exacerbation of their disease, had a higher mean beta 2m ba than those with less active disease. Variations of the serum beta 2m ba occurred especially in patients with active disease but did not seem to reflect the clinical course. The beta 2m ba was recovered in the IgG peak when SLE serum was subjected to gel chromatography on Sephadex G-200.
Topics: Adolescent; Adult; Aged; Chromatography, Gel; Complement C3; Complement C4; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Protein Binding; beta 2-Microglobulin
PubMed: 6370153
DOI: 10.1136/ard.43.2.267 -
International Journal of Molecular... Oct 2021Aggregation of β microglobulin (βm) into amyloid fibrils is associated with systemic amyloidosis, caused by the deposition of amyloid fibrils containing the wild-type...
Aggregation of β microglobulin (βm) into amyloid fibrils is associated with systemic amyloidosis, caused by the deposition of amyloid fibrils containing the wild-type protein and its truncated variant, ΔN6 βm, in haemo-dialysed patients. A second form of familial systemic amyloidosis caused by the βm variant, D76N, results in amyloid deposits in the viscera, without renal dysfunction. Although the folding and misfolding mechanisms of β microglobulin have been widely studied in vitro and in vivo, we lack a comparable understanding of the molecular mechanisms underlying toxicity in a cellular and organismal environment. Here, we established transgenic lines expressing wild-type (WT) human βm, or the two highly amyloidogenic naturally occurring variants, D76N βm and ΔN6 βm, in the bodywall muscle. Nematodes expressing the D76N βm and ΔN6 βm variants exhibit increased age-dependent and cell nonautonomous proteotoxicity associated with reduced motility, delayed development and shortened lifespan. Both βm variants cause widespread endogenous protein aggregation contributing to the increased toxicity in aged animals. We show that expression of βm reduces the capacity of to cope with heat and endoplasmic reticulum (ER) stress, correlating with a deficiency to upregulate BiP/ transcripts in response to ER stress in young adult animals. Interestingly, protein secretion in all βm variants is reduced, despite the presence of the natural signal sequence, suggesting a possible link between organismal βm toxicity and a disrupted ER secretory metabolism.
Topics: Animals; Caenorhabditis elegans; Endoplasmic Reticulum Stress; Heat-Shock Response; Humans; Longevity; Mutation; Protein Aggregates; Unfolded Protein Response; beta 2-Microglobulin
PubMed: 34639093
DOI: 10.3390/ijms221910752 -
Blood Oct 1999Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent... (Comparative Study)
Comparative Study
Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-alpha receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as beta(2)-microglobulin (beta(2)m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. beta(2)m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2)m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of beta(2)m as an apoptosis-inducing factor.
Topics: Amino Acid Chloromethyl Ketones; Amino Acid Sequence; Animals; Antibodies, Monoclonal; Apoptosis; Culture Media, Conditioned; Cysteine Proteinase Inhibitors; Fas Ligand Protein; HL-60 Cells; Humans; K562 Cells; Membrane Glycoproteins; Mice; Molecular Sequence Data; Neoplasm Proteins; Oligopeptides; Receptors, Tumor Necrosis Factor; Sequence Alignment; Sequence Homology, Amino Acid; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; U937 Cells; beta 2-Microglobulin; fas Receptor
PubMed: 10515878
DOI: No ID Found