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Proceedings of the National Academy of... Aug 1979beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized...
beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized as a precursor with an NH2-terminal extension of 19 amino acids: Ser-X-Ser-Val-X-Leu-Val-Phe-Leu-Val-Leu-Val-Ser-Leu-X-Gly-Leu-Tyr-X. The processing and segregation of this peripheral membrane protein are directly comparable to those of secretory proteins and integral membrane proteins: addition of dog pancreas microsomal membranes during translation caused conversion to the processed chain, but addition of membranes after synthesis did not; only the processed chain sedimented with the membrane vesicles and was protected from proteolysis by the vesicles; and processing of nascent beta 2-microglobulin was blocked by competitive inhibitors that prevent processing and segregation of secretory and integral membrane proteins. These results suggest that the signal sequences of secretory proteins, integral membrane proteins, and peripheral membrane proteins have a common function and a common receptor on the cytoplasmic face of dog pancreas microsomal membranes. This system also provides a means for studying in vitro the expression and function of the major histocompatibility antigens that are associated with beta 2-microglobulin on cell surfaces.
Topics: Amino Acid Sequence; Animals; Beta-Globulins; Binding Sites; Cell Line; Cell-Free System; Membrane Proteins; Mice; Microsomes; Protein Biosynthesis; Protein Precursors; Reticulocytes; beta 2-Microglobulin
PubMed: 91168
DOI: 10.1073/pnas.76.8.3651 -
Journal of Acquired Immune Deficiency... Aug 2021Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations...
BACKGROUND
Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus.
METHODS
In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus.
RESULTS
At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P < 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [β= -0.02 (95% CI: -0.03 to -0.0002), P < 0.05], fewer cumulative years on zidovudine [β = -0.027 (95% CI: -0.045 to -0.009), P < 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [β = 0.022 (95% CI: 0.0006 to 0.04), P < 0.05].
CONCLUSIONS
Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation.
Topics: Antiretroviral Therapy, Highly Active; Case-Control Studies; HIV Infections; Humans; Longitudinal Studies; Male; Middle Aged; Sex Hormone-Binding Globulin
PubMed: 33990494
DOI: 10.1097/QAI.0000000000002723 -
Frontiers in Endocrinology 2022Sex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our...
BACKGROUND
Sex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12-19 years.
METHODS
The data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.
RESULTS
A total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.
CONCLUSIONS
We found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.
Topics: Adolescent; Bone Density; Estradiol; Female; Gonadal Steroid Hormones; Humans; Male; Nutrition Surveys; Sex Hormone-Binding Globulin; Testosterone
PubMed: 35669686
DOI: 10.3389/fendo.2022.891217 -
Insect Biochemistry and Molecular... Feb 2017Transferrins are secreted proteins that bind iron. The well-studied transferrins are mammalian serum transferrin, which is involved in iron transport, and mammalian...
Transferrins are secreted proteins that bind iron. The well-studied transferrins are mammalian serum transferrin, which is involved in iron transport, and mammalian lactoferrin, which functions as an immune protein. Lactoferrin and lactoferrin-derived peptides have bactericidal activity, and the iron-free form of lactoferrin has bacteriostatic activity due to its ability to sequester iron. Insect transferrin is similar in sequence to both serum transferrin and lactoferrin, and its functions are not well-characterized; however, many studies of insect transferrin indicate that it has some type of immune function. The goal of this study was to determine the specific immune functions of transferrin from Manduca sexta (tobacco hornworm). We verified that transferrin expression is upregulated in response to infection in M. sexta larvae and determined that the concentration of transferrin in hemolymph increases from 2 μM to 10 μM following an immune challenge. It is also present in molting fluid and prepupal midgut fluid, two extracellular fluids with immune capabilities. No immune-induced proteolytic cleavage of transferrin in hemolymph was observed; therefore, M. sexta transferrin does not appear to be a source of antimicrobial peptides. Unlike iron-saturated lactoferrin, iron-saturated transferrin had no detectable antibacterial activity. In contrast, 1 μM iron-free transferrin inhibited bacterial growth, and this inhibition was blocked by supplementing the culture medium with 1 μM iron. Our results suggest that M. sexta transferrin does not have bactericidal activity, but that it does have a bacteriostatic function that depends on its iron sequestering ability. This study supports the hypothesis that insect transferrin participates in an iron withholding strategy to protect insects from infectious bacteria.
Topics: Animals; Extracellular Fluid; Iron; Manduca; Microbial Sensitivity Tests; Transferrin
PubMed: 27986638
DOI: 10.1016/j.ibmb.2016.12.006 -
Blood Mar 2018
Topics: Child; Coagulation Protein Disorders; Humans; Plasminogen
PubMed: 29567753
DOI: 10.1182/blood-2018-01-828194 -
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 -
Cell Research Feb 2020
Topics: Blood Coagulation; Blood Coagulation Factors; Transferrin
PubMed: 31953530
DOI: 10.1038/s41422-020-0275-z -
The Tohoku Journal of Experimental... Dec 1981Significantly increased levels of plasma beta-thromboglobulin (beta-TG) (76.8 +/- 25.5 ng/ml, p less than 0.01) were observed in 24 patients with chronic renal failure...
Significantly increased levels of plasma beta-thromboglobulin (beta-TG) (76.8 +/- 25.5 ng/ml, p less than 0.01) were observed in 24 patients with chronic renal failure (blood urea nitrogen (BUN) greater than 20 mg/100 ml), as compared with normal subjects (13.2 +/- 5.6 ng/ml). The increase in beta-TG was highly correlated with BUN (r = 0.651, p less than 0.01), creatinine (r = 0.778, p less than 0.01) and creatinine clearance ( t = -0.723, p less than 0.01). Plasma platelet factor 4 (PF4) and normal 5.0 +/- 2.0 ng/ml) also increased significantly to 8.5 +/- 3.4 ng/ml (p less than 0.01). However, statistical correlation between beta-TG and PF4 was not found in these patients. The reason is thought to be due to differences in molecular weight (PF4 8,000 MW; beta-TG 36,000 MW) and half-life time (PF4 30 min; beta-TG 100 min), and due to the difficulty in calculating statistically the correlation because of the narrow distribution of PF4 levels. The high levels of beta-TG (89.4 +/- 3.4 ng/ml) showed a further increase (109.4 +/- 5.8 ng/100 ml, p less than 0.01) after dialysis. This is thought to be due to hemoconcentration, because other blood factors such as RBC, WBC, platelets, fibrinogen, etc were elevated by about 20% during hemodialysis and because no adhesion of platelets to the cellulose membrane did occur. The increase in PF4 levels at 15 min (55.2 +/- 19.6 ng/ml, p less than 0.01) and 1 hr (23.7 +/- 8.4 ng/ml, p less than 0.01) of hemodialysis from the level before it (7.7 +/- 1.3 ng/ml) is thought to be caused the effect of heparin infusion. The change in PF4 was not accompanied by the change in beta-TG. During hemodialysis the decrease of other platelet functions such as adhesiveness, aggregation induced by ADP, collagen and PF3 remained unchanged.
Topics: Adult; Beta-Globulins; Blood Cell Count; Blood Coagulation Factors; Female; Humans; Kidney Failure, Chronic; Male; Platelet Aggregation; Platelet Factor 4; Renal Dialysis; beta-Thromboglobulin
PubMed: 6175048
DOI: 10.1620/tjem.135.349 -
Deutsches Arzteblatt International Jun 2022
Topics: Humans; Transferrin
PubMed: 36106878
DOI: 10.3238/arztebl.m2022.0137 -
Immunobiology Jul 2022The complement system does not only play an important role in the defence against microorganism and pathogens, but also contributes to the regulation of innate and...
The complement system does not only play an important role in the defence against microorganism and pathogens, but also contributes to the regulation of innate and adaptive immunity. Especially activation fragments C3a and C5a and complement activation at the interface of antigen presenting cell (APC) and T cell, were shown to have a role in T cell activation and proliferation. Whereas most complement factors are produced by the liver, properdin, a positive regulator of the C3 convertase, is mainly produced by myeloid cells. Here we show that properdin can be detected in myeloid cell infiltrate during human renal allograft rejection. In vitro, properdin is produced and secreted by human immature dendritic cells (iDCs), which is further increased by CD40-L-matured DCs (mDCs). Transfection with a specific properdin siRNA reduced properdin secretion by iDCs and mDCs, without affecting the expression of co-stimulatory markers CD80 and CD86. Co-culture of properdin siRNA-transfected iDCs and mDCs with human allogeneic T cells resulted in reduced T cell proliferation, especially under lower DC-T cell ratio's (1:30 and 1:90 ratio). In addition, T cell cytokines were altered, including a reduced TNF-α and IL-17 secretion by T cells co-cultured with properdin siRNA-transfected iDCs. Taken together, these results indicate a local role for properdin during the interaction of DCs and allogeneic T cells, contributing to the shaping of T cell proliferation and activation.
Topics: Cells, Cultured; Dendritic Cells; Humans; Kidney Transplantation; Properdin; RNA, Small Interfering; T-Lymphocytes
PubMed: 35843030
DOI: 10.1016/j.imbio.2022.152246