Structural comparison of rat α1- and α2-macroglobulins

Schaeufele, J; Koo, Peter H.

doi:10.1016/0006-291x(82)91823-x

Cited by 35 publications

(23 citation statements)

References 15 publications

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“…The primary sequences of α2M and α1I3 share a 58% homology [1]. Rat α2M is antigenically [2]and structurally [3, 4]more closely related to human α2M than α1M. In normal rats, the rat-specific α1I3 is the most abundant plasma protein besides albumin, with standard concentrations in the range of 6–10 mg/ml [5].…”

Section: Introductionmentioning

confidence: 99%

Alpha Macroglobulins and the Low-Density-Lipoprotein-Related Protein/Alpha-2-Macroglobulin Receptor in Experimental Renal Fibrosis

Goor

Ding

Ga³

1999

Nephron Exp Nephrol

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In this study, we evaluated the location of non-specific proteinase inhibitors and their receptor in experimental glomerular and interstitial fibrosis. The alpha macroglobulins alpha-2-macroglobulin (α2M) and alpha-1-inhibitor 3 (α1I3) are proteinase inhibitors, including metalloproteinases and serine proteases. Using immunohistochemistry, we detected α1I3 in the glomerular mesangium in control rats. In acute and chronic fibrosis, the α1I3 protein expression was dramatically increased throughout the glomerulus and at sites of increased extracellular matrix deposition in the interstitium. The presence of α1I3 in normal and nephrotic kidneys was confirmed by Western blotting. Under chemically reducing conditions, we found that, in contrast to native α1I3, kidney-derived α1I3 has reacted upon by proteinases, thereby revealing a functional role for this macroglobulin under normal and pathological conditions. Double staining revealed that high amounts of glomerular α1I3 were present in sclerotic lesions. α2M was absent in glomeruli and interstitium from control rats, but present in small amounts in glomerular mesangial areas of acute nephrotic rats. α2M was also present in significant amounts in glomeruli from rats with chronic fibrosis. The receptor mediating the uptake of proteinase inhibitor-proteinase complexes, the low-density-lipoprotein-related protein/alpha-2-macroglobulin receptor, was found in the glomerular mesangium and tubulo-interstitium from control rats. Significant increments in receptor expression were found in glomeruli and interstitium of rats with chronic fibrosis, with a preferential localization in fibrotic areas. Interstitial staining for low-density-lipoprotein-related protein/alpha-2-macroglobulin receptor was attributed to fibroblasts, since double staining ruled out dendritic cells and macrophages. In conclusion, these studies demonstrate the intrarenal presence of plasma-derived proteinase inhibitors together with their receptors. These findings may point to a novel mechanism for renal fibrosis wherein matrix-degrading proteinases are inhibited, resulting in renal fibrosis.

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Section: Introductionmentioning

confidence: 99%

Alpha Macroglobulins and the Low-Density-Lipoprotein-Related Protein/Alpha-2-Macroglobulin Receptor in Experimental Renal Fibrosis

Goor

Ding

Ga³

1999

Nephron Exp Nephrol

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“…Rat ␣ 2 M, on the other hand, occurs only in trace amounts in tissues under normal conditions, but its concentration is greatly elevated during inflammation (Ͼ 2 mg/ml in plasma); hence it is an acute-phase protein (Ganrot, 1973;Schaeufele and Koo, 1982;LonbergHolm et al, 1987b). ␣ 1 M shares 57% overall amino acid sequence identity with rat ␣ 2 M (Eggertsen et al, 1991), but rat ␣ 2 M is much more similar to human ␣ 2 M in both antigenic property and subunit structure than ␣ 1 M, albeit human ␣ 2 M is not an acute-phase protein (Schaeufele and Koo, 1982). Aside from some structural and functional characteristics, essentially nothing is known regarding the physiological roles of these rat macroglobulins.…”

Section: Introductionmentioning

confidence: 95%

“…Rat ␣ 1 M and ␣ 2 M were, respectively, prepared from normal and acute-phase plasma as previously described with slight modifications (Schaeufele and Koo, 1982). Briefly, to obtain acute-phase plasma, adult rats (SpragueDawley, 250-400 gm) were injected intramuscularly with turpentine and bled 2 days later.…”

Section: Rat Alpha-macroglobulin Purification and Activation By Monoamentioning

confidence: 99%

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Inhibition of dopamine and choline acetyltransferase concentrations in rat CNS neurons by rat ?1- and ?2-macroglobulins

Liebl

Dluzen

et al. 1998

J. Neurosci. Res.

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Previous studies have implicated human alpha-2-macroglobulin (alpha2M) as a potential regulator of neuronal development and function. Rat alpha-1-macroglobulin (alpha1M) and acute-phase alpha-2-macroglobulin (alpha2M) are murine homologues of human alpha2M. In this report, we tested the effect of intracranially infused serotonin-activated rat alpha1M (5HT-alpha1M) on the concentration of dopamine (DA) in the corpus striatum in vivo and the effect of 5HT-activated rat alpha1M and alpha2M on the choline acetyltransferase (ChAT) activity upon embryonic basal forebrain neurons in culture. The results show that direct infusion of 0.65 nmole rat 5HT-alpha1M into the adult rat corpus striatum produced a consistent attenuation upon striatal DA concentrations. This decrease was particularly prominent at 5-7 days post-infusion. In addition, rat 5HT-alpha1M and rat 5HT-alpha2M, like human 5HT-alpha2M, all significantly inhibited ChAT activity of embryonic rat cerebral cortex neurons. Although normal human alpha2M and rat alpha2M were either marginally or insignificantly inhibitory in this preparation, normal rat alpha1M dose-dependently inhibited ChAT activity. These results demonstrate that monoamine-activated alpha-macroglobulins from rat depress dopaminergic and cholinergic neurotransmitter systems in the CNS, and this suggests a potential regulatory role of these alpha-macroglobulins in neurotransmitter metabolism.

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“…The serum concentration of a2-macroglobulin may increase up to 1000-fold [8, 91, whereas that of al-inhibitor 3 undergoes a 70% reduction [lo]. In contrast, the serum level of al-macroglobulin remains virtually unchanged during acute inflammation [l 11. cDNA clones for a,-macroglobulin have led to the elucidation of the molecular basis of its physiological reaction response [9, 121. Apparently, the regulation of a2-macroglobulin is at the level of mRNA synthesis.…”

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confidence: 99%

Identification and sequencing of cDNA clones for the rodent negative acute‐phase protein α₁‐inhibitor 3

Schweizer

Takabayashi

Geiger

et al. 1987

European Journal of Biochemistry

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Rat α1‐inhibitor 3 clones were isolated by immunological screening of a λ gt11 cDNA library prepared from rat liver poly(A)‐rich RNA. The recombinant cDNA clones were identified by the absence of their immunoprecipitable products following hybrid‐arrested in vitro translation. The size of the cognate poly(A)‐rich RNA was estimated to be roughly 5000 residues. Approximately 16 h after induction of inflammation the amount of α1‐inhibitor 3 poly(A)‐rich RNA decreases as shown by dot‐blot hybridization and Northern analyses. The response of this negative acute‐phase plasma protein to inflammation may therefore be considered to be at the pretranslational level. The characterized DNA constitutes an open reading frame of 225 amino acids followed by a canonical eucaryotic polyadenylation signal and a poly(A) tail. Sequence microheterogeneity, particularly in the 3′‐flanking region was observed. An amino acid homology of 70% for α1‐inhibitor 3 with human and rodent α2‐macroglobulin emphasizes the evolutionary relationship of the macroglobulins.

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Structural comparison of rat α1- and α2-macroglobulins

Cited by 35 publications

References 15 publications

Alpha Macroglobulins and the Low-Density-Lipoprotein-Related Protein/Alpha-2-Macroglobulin Receptor in Experimental Renal Fibrosis

Alpha Macroglobulins and the Low-Density-Lipoprotein-Related Protein/Alpha-2-Macroglobulin Receptor in Experimental Renal Fibrosis

Inhibition of dopamine and choline acetyltransferase concentrations in rat CNS neurons by rat ?1- and ?2-macroglobulins

Identification and sequencing of cDNA clones for the rodent negative acute‐phase protein α₁‐inhibitor 3

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Structural comparison of rat α1- and α2-macroglobulins

Cited by 35 publications

References 15 publications

Alpha Macroglobulins and the Low-Density-Lipoprotein-Related Protein/Alpha-2-Macroglobulin Receptor in Experimental Renal Fibrosis

Alpha Macroglobulins and the Low-Density-Lipoprotein-Related Protein/Alpha-2-Macroglobulin Receptor in Experimental Renal Fibrosis

Inhibition of dopamine and choline acetyltransferase concentrations in rat CNS neurons by rat ?1- and ?2-macroglobulins

Identification and sequencing of cDNA clones for the rodent negative acute‐phase protein α1‐inhibitor 3

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Identification and sequencing of cDNA clones for the rodent negative acute‐phase protein α₁‐inhibitor 3