Discoordinate hormonal and ontogenetic regulation of four rat serpin genes

1992 ◽  
Vol 262 (5) ◽  
pp. C1144-C1148 ◽  
Author(s):  
S. J. Schwarzenberg ◽  
J. B. Yoon ◽  
S. Seelig ◽  
C. J. Potter ◽  
S. A. Berry
Keyword(s):  
Growth Hormone ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Age Group ◽  
Serum Growth Hormone ◽  
Physiological Conditions ◽  
Specific Mrnas ◽  
Alpha 1 Antitrypsin ◽  
Inhibitor Genes

To understand the roles of four highly homologous rat hepatic serine protease inhibitor genes (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin), we measured the hepatic content of their specific mRNAs under several physiological conditions. Spi 2.1 and 2.3 mRNAs, which are regulated by growth hormone, paralleled serum growth hormone levels developmentally. Only Spi 2.1 mRNA decreased with starvation, while Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs did not change. Despite the close homology of the Spi genes to mouse contrapsin, which is regulated by testosterone, none of the serine protease inhibitor mRNAs examined here was dependent on androgens for expression. Spi 2.2 mRNA displayed a unique ontogenetic regulation, with a rise in hepatic content at day 19 to levels five times that of any other age group. These studies confirm the importance of growth hormone in the regulation of Spi 2.1 and 2.3 mRNAs and suggest that Spi 2.2 mRNA may be regulated by metabolic alterations occurring in the weaning period.

scholarly journals Analysis of proteins binding to the proximal promoter region of two rat serine protease inhibitor genes

1992 ◽  
Vol 20 (5) ◽  
pp. 1061-1068 ◽  
Author(s):  
Valerie Rossi ◽  
Jean Francois Rouayrenc ◽  
Laurent Paquereau ◽  
Marie Joseé Vilarem ◽  
Alphonse Le Cam
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Promoter Region ◽  
Serine Protease Inhibitor ◽  
Proximal Promoter ◽  
Proximal Promoter Region ◽  
Inhibitor Genes

scholarly journals Genome-Wide Identification and Immune Response Analysis of Serine Protease Inhibitor Genes in the Silkworm, Bombyx mori

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31168 ◽  
Author(s):  
Ping Zhao ◽  
Zhaoming Dong ◽  
Jun Duan ◽  
Genhong Wang ◽  
Lingyan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Protease Inhibitor ◽  
Bombyx Mori ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Response Analysis ◽  
Genome Wide ◽  
Inhibitor Genes ◽  
Silkworm Bombyx Mori

scholarly journals Modulation of the Growth Hormone Response of the Serine Protease Inhibitor 2.1 Gene by Cytokines in Rat Hepatocytes

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 85A-85A
Author(s):  
S A Berry ◽  
P L Bergad ◽  
S J Schwarzenberg ◽  
S Amarasinghe ◽  
H C Towle
Keyword(s):  
Growth Hormone ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Rat Hepatocytes ◽  
Serine Protease Inhibitor ◽  
Growth Hormone Response ◽  
Hormone Response

scholarly journals Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2–Priming Protease TMPRSS2

2021 ◽  
Vol 6 (1) ◽  
pp. 55-74
Author(s):  
Nurit P Azouz ◽  
Andrea Klingler ◽  
Victoria Callahan ◽  
Ivan Akhrymuk ◽  
Katarina Elez ◽  
...  
Keyword(s):  
Viral Load ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Inhibitory Activity ◽  
Serine Proteases ◽  
Serine Protease Inhibitor ◽  
Host Cells ◽  
S Protein ◽  
Relative Contribution ◽  
Alpha 1 Antitrypsin

Background: Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry.  Methods: We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems. Results: We identified the human extracellular serine protease inhibitor (serpin) alpha 1 antitrypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity.  Conclusions: Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.

scholarly journals Ethnic differences in SERPINA1 allele frequencies may partially explain national differences in COVID-19 fatality rates

2020 ◽  
Author(s):  
Guy Shapira ◽  
Noam Shomron ◽  
David Gurwitz
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Ethnic Differences ◽  
Serine Protease Inhibitor ◽  
Preliminary Evidence ◽  
Allele Frequencies ◽  
National Differences ◽  
Alpha 1 Antitrypsin

COVID-19 infection and fatality rates vary considerably between countries. We present preliminary evidence that these variations may in part reflect ethnic differences in the frequencies of polymorphic alleles of SERPINA1, coding for alpha-1 antitrypsin, the major blood serine protease inhibitor.

scholarly journals Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2–Priming Protease TMPRSS2

2020 ◽  
Author(s):  
Nurit P. Azouz ◽  
Andrea M. Klingler ◽  
Victoria Callahan ◽  
Ivan V. Akhrymuk ◽  
Katarina Elez ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Cell Entry ◽  
Host Cells ◽  
Extracellular Proteases ◽  
S Protein ◽  
Protein Priming ◽  
Alpha 1 Antitrypsin ◽  
Extracellular Serine Protease

AbstractHost proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry. The main cellular location where the SARS-CoV-2 S protein priming occurs remains debatable, therefore hampering the development of targeted treatments. Herein, we identified the human extracellular serine protease inhibitor (serpin) alpha 1 antitrypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease–inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity. Our data support the key role of extracellular serine proteases in SARS-CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.SummaryDelivery of extracellular serine protease inhibitors (serpins) such as A1AT has the capacity to reduce SARS-CoV-2 dissemination by binding and inhibiting extracellular proteases on the host cells, thus, inhibiting the first step in SARS-CoV-2 cell cycle (i.e. cell entry).

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