Inhibition of human serine proteases by SPAAT, the C-terminal 44-residue peptide from α1-antitrypsin

Niemann, Marilyn A.; Baggott, Joseph E.; Miller, Edward J.

doi:10.1016/s0167-4838(97)00034-4

Cited by 11 publications

(11 citation statements)

References 26 publications

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“…A1AT is abundant in human placental tissue compartments (60,61). It has been proposed that progressive proteolytic cleavage of A1AT occurs in the placenta, and proteases that mediate enzymatic fragmentation of A1AT to A1ATm 358 in vitro are known (39,62,63), although a specific placental protease has not been identified. A protease that is increased in human placental syncytiotrophoblasts in the third trimester of pregnancy, high temperature requirement protease 1, cleaves A1AT in the carboxy terminus (61).…”

Section: Discussionmentioning

confidence: 99%

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation

Yost

Schwertz

Cody

et al. 2016

Journal of Clinical Investigation

119

133

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Section: Discussionmentioning

confidence: 99%

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation

Yost

Schwertz

Cody

et al. 2016

Journal of Clinical Investigation

119

133

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“…This novel site may also inactivate of the intact inhibitor or the C-terminal fragment (e.g., residues 375-408), which has also been shown to act as a protease inhibitor. 69 The peptides from inter-R-trypsin inhibitor H4 (ITH4) are also instructive. In a recent publication, 3 a single peptide cleaved from inter-R-trypsin inhibitor H4 (ITH4), 658-MNFR-PGVLSSRQLGLPGPPDVPDHAAYHPF-687, with m/z 3,272 has been reported to be a valuable marker for ovarian cancer when used in combination with CA125.…”

Section: Research Articlesmentioning

confidence: 99%

Direct Tandem Mass Spectrometry Reveals Limitations in Protein Profiling Experiments for Plasma Biomarker Discovery

et al. 2005

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The low molecular weight plasma proteome and its biological relevance are not well defined; therefore, experiments were conducted to directly sequence and identify peptides observed in plasma and serum protein profiles. Protein fractionation, matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) profiling, and liquid-chromatography coupled to MALDI tandem mass spectrometry (MS/MS) sequencing were used to analyze the low molecular weight proteome of heparinized plasma. Four fractionation techniques using functionally derivatized 96-well plates were used to extract peptides from plasma. Tandem TOF was successful for identifying peptides up to m/z 5500 with no prior knowledge of the sequence and was also used to verify the sequence assignments for larger ion signals. The peptides (n>250) sequenced in these profiles came from a surprisingly small number of proteins (n approximately 20), which were all common to plasma, including fibrinogen, complement components, antiproteases, and carrier proteins. The cleavage patterns were consistent with those of known plasma proteases, including initial cleavages by thrombin, plasmin and complement proteins, followed by aminopeptidase and carboxypeptidase activity. On the basis of these data, we discuss limitations in biomarker discovery in the low molecular weight plasma or serum proteome using crude fractionation coupled to MALDI-MS profiling.

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“…Therefore, the 44 aa peptides are expected to contain the active site region and protease inhibitory activity. In support, the 44-residue C-terminal fragment of A1AT detected in placenta and human tissues [34], was found to inhibit neutrophil and pancreatic elastases [35]. …”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene

et al. 2017

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Human SERPINA1 gene is located on chromosome 14q31-32.3 and is organized into three (IA, IB, and IC) non-coding and four (II, III, IV, V) coding exons. This gene produces α1-antitrypsin (A1AT), a prototypical member of the serpin superfamily of proteins. We demonstrate that human peripheral blood leukocytes express not only a product corresponding to the transcript coding for the full-length A1AT protein but also two short transcripts (ST1C4 and ST1C5) of A1AT. In silico sequence analysis revealed that the last exon of the short transcripts contains an Open Reading Frame (ORF) and thus putatively can produce peptides. We found ST1C4 expression across different human tissues whereas ST1C5 was mainly restricted to leukocytes, specifically neutrophils. A high up-regulation (10-fold) of short transcripts was observed in isolated human blood neutrophils after activation with lipopolysaccharide. Parallel analyses by liquid chromatography-mass spectrometry identified peptides corresponding to C-terminal region of A1AT in supernatants of activated but not naïve neutrophils. Herein we report for the first time a tissue specific expression and regulation of short transcripts of SERPINA1 gene, and the presence of C-terminal peptides in supernatants from activated neutrophils, in vitro. This gives a novel insight into the studies on the transcription of SERPINA1 gene.

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Inhibition of human serine proteases by SPAAT, the C-terminal 44-residue peptide from α1-antitrypsin

Cited by 11 publications

References 26 publications

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation

Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation

Direct Tandem Mass Spectrometry Reveals Limitations in Protein Profiling Experiments for Plasma Biomarker Discovery

Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene

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