Serum α2-macroglobulin concentration and its variation with age and sex

Ganrot, P. O.; Scherstén, Bengt

doi:10.1016/0009-8981(67)90333-6

Cited by 146 publications

(44 citation statements)

References 14 publications

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“…It has been known since the 1960s that alpha2-macoglobulin, the third most abundant protein in blood plasma, is present in adult female samples at an approximately 15% higher concentration than in adult male samples (16). We decided to look for sex differences among 70 to 100 of the most abundant proteins, because there are only a few reports in the literature of studies on sex differentiation via proteomics blood analysis (17,18), none of which used label-free quantification.…”

Section: Resultsmentioning

confidence: 99%

In Silico Instrumental Response Correction Improves Precision of Label-free Proteomics and Accuracy of Proteomics-based Predictive Models

Lyutvinskiy

Yang

Rutishauser

et al. 2013

Molecular & Cellular Proteomics

131

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In the analysis of proteome changes arising during the early stages of a biological process (e.g. disease or drug treatment) or from the indirect influence of an important factor, the biological variations of interest are often small (ϳ10%). The corresponding requirements for the precision of proteomics analysis are high, and this often poses a challenge, especially when employing label-free quantification. One of the main contributors to the inaccuracy of label-free proteomics experiments is the variability of the instrumental response during LC-MS/MS runs. Such variability might include fluctuations in the electrospray current, transmission efficiency from the air-vacuum interface to the detector, and detection sensitivity. We have developed an in silico post-processing method of reducing these variations, and have thus significantly improved the precision of label-free proteomics analysis. For abundant blood plasma proteins, a coefficient of variation of approximately 1% was achieved, which allowed for sex differentiation in pooled samples and Ϸ90% accurate dif- Label-free proteomics is sensitive, comprehensive, and versatile (1, 2). The "lyse, digest, and analyze" approach requires the least sample preparation and wet chemistry of all quantitative proteomics approaches (3). The label-free quantification technique is equally applicable to the analysis of peptide mixtures, protein complexes, body fluid proteomes, whole organisms, organs, and organelles. It also does not impose a limitation on the number of samples, which makes it best suited for the requirements of clinical proteomics in which analyses of large cohorts are common. Additionally, a single LC-MS/MS run can identify and quantify several thousand proteins, which makes the cost of analysis per quantified peptide, protein, or proteome very low (4).A significant drawback of label-free proteomics has been its limited precision in the determination of relative changes in peptide abundance, even when the area of the extracted chromatographic peak is used as the peptide abundance. It has been estimated that such label-free quantification gives abundance ratio results that are on average two to three times less accurate than the "gold standard" in global proteomics, stable isotope labeling of amino acids in cell culture (SILAC) 1 (4). There are several reasons for such a performance gap. Unlike in SILAC, where proteins in all samples under comparison are extracted and digested simultaneously (5, 6), in the label-free method, each sample is prepared independently, and therefore variations in sample preparation conditions can cause abundance fluctuations. However, these variations are a subjective factor that can be reduced by training the personnel and/or by employing sample preparation robots. The main objective contributor to the imprecision of a label-free LC-MS/MS experiment is the fluctuation of the instrumental response during the LC-MS/MS run or series of runs. A major component of the instrumental response fluctuation is the variation in the current...

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Section: Resultsmentioning

confidence: 99%

In Silico Instrumental Response Correction Improves Precision of Label-free Proteomics and Accuracy of Proteomics-based Predictive Models

Lyutvinskiy

Yang

Rutishauser

et al. 2013

Molecular & Cellular Proteomics

131

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“…Patients with chronic renal disease and chronic renal disease with hypoalbuminemia had less striking but significant elevations of a-2-macroglobulin, with mean levels of 533 and 399 mg/100 ml, respectively (Fig. 1), even where variations due to age and sex were considered [8]. There was an inverse relation between a-2-macroglobulin and albumin concentration (r = -0.905, P < 0.001), for all samples; this relation could not be demonstrated when a-2-macroglobulin values were in the normal range (r = 0.136, P not significant).…”

Section: A-2-macroglobulin and Antifibrinolysinmentioning

confidence: 99%

Fibrinolytic Studies in the Nephrotic Syndrome

Scheinman

Stiehm

1971

Pediatr Res

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“…Proteins of the az-macroglobulin (a,M) family are abundant components in the plasma of mammals (Sottrup-Jensen, 1987, 1989 and arthropods (Armstrong et al, 1996;, comprising about 3% of the total plasma protein of humans (Ganrot and Schersten, 1967) and the third most abundant protein in the plasma of the American horseshoe crab, Linzulzcs polyphemus Ci,r.r.f,sl,o~zde,zc.e …”

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confidence: 99%

“…Furthermore, immunoblotting of large and small granules of the hemocytes with antiserum against a,M indicated the presence of the cx,M in large granules. Trypsintreated Linzu/us a2M, but not the native a2M, displaced methylamine-treated human ' "51-u2M from the human cx,M receptor with a Kd of 30 nM, suggesting conservation of the proteinase-clearance mechanisms between mammalian and arthropod evolutionary lineages.Keyuvrds: u2-macroglobulin; horseshoe crab; invertebrate; cDNA.Proteins of the az-macroglobulin (a,M) family are abundant components in the plasma of mammals (Sottrup-Jensen, 1987, 1989 and arthropods (Armstrong et al, 1996;, comprising about 3% of the total plasma protein of humans (Ganrot and Schersten, 1967) and the third most abundant protein in the plasma of the American horseshoe crab, Linzulzcs polyphemus Ci,r.r.f,sl,o~zde,zc.e …”

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confidence: 99%

Molecular Cloning of Limulusα₂‐Macroglobulin

Iwaki

Kawabata

Miura

et al. 1996

European Journal of Biochemistry

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The American horseshoe crab Limulus polyphemus contains a,-macroglobulin (a,M) in the hemolymph plasma and hemocytes. a,M from Lirnulus shows many of the typical characteristics of mammalian a,M, including the presence of an internal thiol-ester, reactivity with a diversity of endopeptidases, a unique proteinase-trapping mechanism, and reactivity with the mammalian a,M receptor. Additionally, Limulus rx, M has the unique property that it regulates the limulin-based hemolytic system of the plasma.A cDNA encoding Limulus a,M has been obtained from a hemocyte cDNA library. The open reading frame encodes an N-terminal signal sequence of 25 amino acid residues and a mature protein of 1482 residues. The entire amino acid sequence is similar to those of the mammalian uZMs (28-29% identity) and contains common features found in mammalian a,Ms, a bait region, an internal thiol-ester site, and a receptor-binding domain. However, the N-terminal portion (positions 24-105) has no sequence similarity with those of mammalian a,Ms, and it is structurally related to that of the human complement factor C8y chain, consistent with a role for Limulus a,M in host defense. The component sugar analysis of Limulus a,M showed the existence of a complex type of oligosaccharide chain similar to those of mammalian u,M. However, unlike mammalian m2M, no sialic acid was detected in Limulus rx,M and it contained approximately 3 mol/mol N-acetylgalactosamine, suggesting the presence of 0-linked sugar chains, which have not been found in mammalian n,M.Expression of a,M was detected in hemocyies, but not in hepatopancreas, heart, stomach, intestine, coxal gland, brain and skeletal muscle. Furthermore, immunoblotting of large and small granules of the hemocytes with antiserum against a,M indicated the presence of the cx,M in large granules. Trypsintreated Linzu/us a2M, but not the native a2M, displaced methylamine-treated human ' "51-u2M from the human cx,M receptor with a Kd of 30 nM, suggesting conservation of the proteinase-clearance mechanisms between mammalian and arthropod evolutionary lineages.Keyuvrds: u2-macroglobulin; horseshoe crab; invertebrate; cDNA.Proteins of the az-macroglobulin (a,M) family are abundant components in the plasma of mammals (Sottrup-Jensen, 1987, 1989 and arthropods (Armstrong et al., 1996;, comprising about 3% of the total plasma protein of humans (Ganrot and Schersten, 1967) and the third most abundant protein in the plasma of the American horseshoe crab, Linzulzcs polyphemus Ci,r.r.f,sl,o~zde,zc.e

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Serum α2-macroglobulin concentration and its variation with age and sex

Cited by 146 publications

References 14 publications

In Silico Instrumental Response Correction Improves Precision of Label-free Proteomics and Accuracy of Proteomics-based Predictive Models

In Silico Instrumental Response Correction Improves Precision of Label-free Proteomics and Accuracy of Proteomics-based Predictive Models

Fibrinolytic Studies in the Nephrotic Syndrome

Molecular Cloning of Limulusα₂‐Macroglobulin

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Serum α2-macroglobulin concentration and its variation with age and sex

Cited by 146 publications

References 14 publications

In Silico Instrumental Response Correction Improves Precision of Label-free Proteomics and Accuracy of Proteomics-based Predictive Models

In Silico Instrumental Response Correction Improves Precision of Label-free Proteomics and Accuracy of Proteomics-based Predictive Models

Fibrinolytic Studies in the Nephrotic Syndrome

Molecular Cloning of Limulusα2‐Macroglobulin

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Molecular Cloning of Limulusα₂‐Macroglobulin