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Gene Review

Serpina1  -  serpin peptidase inhibitor, clade A (alpha...

Rattus norvegicus

Synonyms: AAT, Alpha-1-antiproteinase, Alpha-1-antitrypsin, Alpha-1-proteinase inhibitor, Pi, ...
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Disease relevance of Serpina1


High impact information on Serpina1


Chemical compound and disease context of Serpina1


Biological context of Serpina1

  • A cDNA clone encoding rat alpha 1-antitrypsin has been isolated from a lambda gt-11 rat liver cDNA library using an antigen-overlay immunoscreening method [10].
  • Surprisingly, although constitutive LF-B1 expression could activate alpha 1AT-CAT transgenes in these cells, it neither prevented nor reversed extinction of the chromosomal alpha 1AT genes [1].
  • This suggested that alpha 1AT extinction in hybrids might be an indirect, lack-of-activation phenotype mediated primarily through repression of LF-B1 [1].
  • Mutations in this region failed to activate alpha 1AT expression in nonhepatic cells, but mutations in the binding site for liver factor B1 (LF-B1) reduced hepatic-specific expression greater than 100-fold [1].
  • Assignment of human alpha 1-antitrypsin to chromosome 14 by somatic cell hybrid analysis [11].

Anatomical context of Serpina1

  • Northern blot analysis using the cDNA probe showed that rat alpha 1-antitrypsin is expressed at high levels in the liver and at low levels in the submandibular gland and the lung.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
  • Normal liver and differentiated hepatoma cell lines contain a nuclear factor, HNF-1, which binds functional sequences within the promoters of the alpha and beta chains of fibrinogen and alpha 1-antitrypsin [12].
  • Human alpha 1-antitrypsin ( alpha-1-AT;Pi) production was analyzed in 11 primary mouse hepatoma-human lymphoid cell hybrids and in 14 secondary rat hepatoma-human fetal liver fibroblast hybrids [11].
  • The in vitro transcription system is tissue-specific in that the AAT promoter is functional in nuclear extracts prepared from the liver but not from HeLa cells [13].
  • Separation of hepatocytes and sinusoidal liver cells from the rat intravenously injected with 125I-labeled AAT isozymes revealed that sinusoidal cells were responsible for the plasma clearances [14].

Associations of Serpina1 with chemical compounds

  • The reactive center sequence of rat alpha 1-antitrypsin is highly conserved with respect to human alpha 1-antitrypsin, both having Met-Ser at the P1 and P1' residues [10].
  • DNA-binding and antisera reactivity data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a DNA-binding activity implicated in the regulation of transcription of the alpha 1-antitrypsin, apolipoprotein A1, and pyruvate kinase genes [15].
  • The specificity of serpin superfamily protease inhibitors such as alpha 1-antitrypsin or C1 inhibitor is determined by the amino acid residues of the inhibitor reactive center [2].
  • Transfected cells were grown in the absence and presence of human GH and dexamethasone for the Spi 2.1 gene construct [16].
  • Two of the cell lines, ALB-6 and ALB-8, expressed all five liver-specific mRNAs studied, albumin, alpha-1-antitrypsin, fibrinogen, alpha-1-acid glycoprotein, and histidase [17].

Regulatory relationships of Serpina1


Other interactions of Serpina1

  • This pattern of expression mirrors the complex pattern of expression of many genes, such as alpha-fetoprotein, alpha 1-antitrypsin, and fibrinogen, whose promoters contain HNF-1 sites [19].
  • Animals mounted both positive and negative acute phase responses at all ages, but responses were blunted in young animals, reaching adult levels by days 7-19. alpha 1-Antitrypsin mRNA had no response, and Spi 2.2 mRNA had 50% the rise seen in adults on days 3 and 7 [20].
  • The same result was obtained when protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) were added to Kupffer cell-conditioned medium (n = 3), thus eliminating the potential effect of matrix degradation [21].
  • Minimal hepatic transit times were 17, 23, and 31 min for albumin, alpha 1-antitrypsin, and transferrin, respectively [22].
  • DPP-IV-positive hepatocyte-like cells also expressed other markers of hepatocytic differentiation, including albumin, transferrin, and alpha-1-antitrypsin, suggesting that the progeny of transplanted WB-F344 cells express a complete hepatocyte differentiation program [23].

Analytical, diagnostic and therapeutic context of Serpina1


  1. Extinction of alpha 1-antitrypsin gene expression in somatic cell hybrids: evidence for multiple controls. Bulla, G.A., DeSimone, V., Cortese, R., Fournier, R.E. Genes Dev. (1992) [Pubmed]
  2. Protection by recombinant alpha 1-antitrypsin Ala357 Arg358 against arterial hypotension induced by factor XII fragment. Schapira, M., Ramus, M.A., Waeber, B., Brunner, H.R., Jallat, S., Carvallo, D., Roitsch, C., Courtney, M. J. Clin. Invest. (1987) [Pubmed]
  3. A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes. Costa, R.H., Grayson, D.R., Xanthopoulos, K.G., Darnell, J.E. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  4. Behavior of genes directly injected into the rat heart in vivo. Buttrick, P.M., Kass, A., Kitsis, R.N., Kaplan, M.L., Leinwand, L.A. Circ. Res. (1992) [Pubmed]
  5. Angiotensinogen is related to the antitrypsin-antithrombin-ovalbumin family. Doolittle, R.F. Science (1983) [Pubmed]
  6. Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells. Geisterfer, A.A., Owens, G.K. Hypertension (1989) [Pubmed]
  7. Alpha 1-antitrypsin protects neonatal rats from pulmonary vascular and parenchymal effects of oxygen toxicity. Koppel, R., Han, R.N., Cox, D., Tanswell, A.K., Rabinovitch, M. Pediatr. Res. (1994) [Pubmed]
  8. Regulation of the acute phase response genes alpha 1-acid glycoprotein and alpha 1-antitrypsin correlates with sensitivity to thermal injury. Gilpin, D.A., Hsieh, C.C., Kuninger, D.T., Herndon, D.N., Papaconstantinou, J. Surgery (1996) [Pubmed]
  9. Emphysema induced by intravenously administered endotoxin in an alpha 1-antitrypsin-deficient rat model. Blackwood, R.A., Moret, J., Mandl, I., Turino, G.M. Am. Rev. Respir. Dis. (1984) [Pubmed]
  10. Molecular cloning and primary structure of rat alpha 1-antitrypsin. Chao, S., Chai, K.X., Chao, L., Chao, J. Biochemistry (1990) [Pubmed]
  11. Assignment of human alpha 1-antitrypsin to chromosome 14 by somatic cell hybrid analysis. Darlington, G.J., Astrin, K.H., Muirhead, S.P., Desnick, R.J., Smith, M. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  12. A variant nuclear protein in dedifferentiated hepatoma cells binds to the same functional sequences in the beta fibrinogen gene promoter as HNF-1. Baumhueter, S., Courtois, G., Crabtree, G.R. EMBO J. (1988) [Pubmed]
  13. Multiple hepatic trans-acting factors are required for in vitro transcription of the human alpha-1-antitrypsin gene. Li, Y., Shen, R.F., Tsai, S.Y., Woo, S.L. Mol. Cell. Biol. (1988) [Pubmed]
  14. Plasma clearance of intravenously injected aspartate aminotransferase isozymes: evidence for preferential uptake by sinusoidal liver cells. Kamimoto, Y., Horiuchi, S., Tanase, S., Morino, Y. Hepatology (1985) [Pubmed]
  15. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Sladek, F.M., Zhong, W.M., Lai, E., Darnell, J.E. Genes Dev. (1990) [Pubmed]
  16. Cytoplasmic sequences of the growth hormone receptor necessary for signal transduction. Goujon, L., Allevato, G., Simonin, G., Paquereau, L., Le Cam, A., Clark, J., Nielsen, J.H., Djiane, J., Postel-Vinay, M.C., Edery, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  17. ras transformation of simian virus 40-immortalized rat hepatocytes: an in vitro model of hepatocarcinogenesis. Fang, X.J., Flowers, M., Keating, A., Cameron, R., Sherman, M. Cancer Res. (1992) [Pubmed]
  18. Rat lung tissue is a site of alpha 1-proteinase inhibitor synthesis: evidence by cell-free translation. Budek, W., Bünning, P., Heinrich, P.C. Biochem. Biophys. Res. Commun. (1984) [Pubmed]
  19. HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Baumhueter, S., Mendel, D.B., Conley, P.B., Kuo, C.J., Turk, C., Graves, M.K., Edwards, C.A., Courtois, G., Crabtree, G.R. Genes Dev. (1990) [Pubmed]
  20. Developmental regulation of the hepatic acute phase response. Schwarzenberg, S.J., Potter, C.J., Berry, S.A. Am. J. Physiol. (1991) [Pubmed]
  21. Reversible inhibition of albumin production by rat hepatocytes maintained on a laminin-rich gel (Engelbreth-Holm-Swarm) in response to secretory products of Kupffer cells and cytokines. Kowalski-Saunders, P.W., Winwood, P.J., Arthur, M.J., Wright, R. Hepatology (1992) [Pubmed]
  22. The biosynthesis of rat transferrin. Evidence for rapid glycosylation, disulfide bond formation, and tertiary folding. Morgan, E.H., Peters, T. J. Biol. Chem. (1985) [Pubmed]
  23. Evaluation of the differentiation potential of WB-F344 rat liver epithelial stem-like cells in vivo. Differentiation to hepatocytes after transplantation into dipeptidylpeptidase-IV-deficient rat liver. Coleman, W.B., McCullough, K.D., Esch, G.L., Faris, R.A., Hixson, D.C., Smith, G.J., Grisham, J.W. Am. J. Pathol. (1997) [Pubmed]
  24. Triacylglycerol synthesis by purified triacylglycerol synthetase of rat intestinal mucosa. Role of acyl-CoA acyltransferase. Lehner, R., Kuksis, A. J. Biol. Chem. (1995) [Pubmed]
  25. Differential inhibition of rat mast cell proteinase I and II by members of the alpha-1-proteinase inhibitor family of serine proteinase inhibitors. Pirie-Shepherd, S.R., Miller, H.R., Ryle, A. J. Biol. Chem. (1991) [Pubmed]
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