alpha 1 antichymotrypsin

Summary

Summary: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily.

Top Publications

  1. Billingsley G, Walter M, Hammond G, Cox D. Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1. Am J Hum Genet. 1993;52:343-53 pubmed
    ..These genes form a PI cluster at 14q32.1, similar to that of the homologous genes on murine chromosome l2. The close proximity of these genes has implications for disease-association studies. ..
  2. Stratil A, Peelman L, Mattheeuws M, Van Poucke M, Reiner G, Geldermann H. A novel porcine gene, alpha-1-antichymotrypsin 2 (SERPINA3-2): sequence, genomic organization, polymorphism and mapping. Gene. 2002;292:113-9 pubmed
    ..SERPINA3-2 is the first porcine serpin gene whose genomic organization has been determined. ..
  3. Inglis J, Hill R. The murine Spi-2 proteinase inhibitor locus: a multigene family with a hypervariable reactive site domain. EMBO J. 1991;10:255-61 pubmed
    ..The divergence is also appreciably greater than that occurring in an adjacent non-coding sequence. This phenomenon has established novel potential inhibitory specificities, while maintaining a functional inhibitor structure. ..
  4. Sun Y, Minthon L, Wallmark A, Warkentin S, Blennow K, Janciauskiene S. Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2003;16:136-44 pubmed
  5. DeKosky S, Ikonomovic M, Wang X, Farlow M, Wisniewski S, Lopez O, et al. Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer's disease: correlation with cognitive impairment. Ann Neurol. 2003;53:81-90 pubmed
  6. Poller W, Faber J, Weidinger S, Tief K, Scholz S, Fischer M, et al. A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease. Genomics. 1993;17:740-3 pubmed
    ..These mutations were not detected among 100 healthy control subjects, suggesting a possible pathogenetic role of ACT gene defects in a subset of patients with COPD. ..
  7. Stratil A, Cízová Schröffelová D, Gábrisová E, Pavlik M, Coppieters W, Peelman L, et al. Pig plasma alpha-protease inhibitors PI2, PI3 and PI4 are members of the antichymotrypsin family. Comp Biochem Physiol B Biochem Mol Biol. 1995;111:53-60 pubmed
    ..M29508) revealed great similarities, the sequence of PI2 I being virtually identical with the pig AACT. On the basis of all available results, PI2 is proposed to be pig AACT, an orthologue of human AACT. ..
  8. Musilova P, Lahbib Mansais Y, Yerle M, Cepica S, Stratil A, Coppieters W, et al. Assignment of pig alpha 1-antichymotrypsin (AACT or PI2) gene to chromosome region 7q23-q26. Mamm Genome. 1995;6:445 pubmed
  9. Abraham C, Selkoe D, Potter H. Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Cell. 1988;52:487-501 pubmed
    ..Models by which alpha 1-antichymotrypsin could contribute to the development of Alzheimer amyloid deposits are discussed. ..

More Information

Publications62

  1. Wang X, DeKosky S, Ikonomovic M, Kamboh M. Distribution of plasma alpha 1-antichymotrypsin levels in Alzheimer disease patients and controls and their genetic controls. Neurobiol Aging. 2002;23:377-82 pubmed
    ..In conclusion, ACT may play an important role in the AD pathogenesis and genetic variation in the ACT gene appears to have some effect on plasma ACT concentrations. ..
  2. Kalsheker N, Morley S, Morgan K. Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin. Biochem Soc Trans. 2002;30:93-8 pubmed
    ..100 bp upstream from the transcription initiation site, and a further interleukin-1-responsive enhancer has been identified approx. 13 kb upstream. The pathways for a humoral response are being mapped at high resolution. ..
  3. Forsyth S, Horvath A, Coughlin P. A review and comparison of the murine alpha1-antitrypsin and alpha1-antichymotrypsin multigene clusters with the human clade A serpins. Genomics. 2003;81:336-45 pubmed
    ..In summarizing the literature and suggesting a standardized nomenclature, we aim to provide a logical structure on which future research may be based. ..
  4. Abraham C, Shirahama T, Potter H. Alpha 1-antichymotrypsin is associated solely with amyloid deposits containing the beta-protein. Amyloid and cell localization of alpha 1-antichymotrypsin. Neurobiol Aging. 1990;11:123-9 pubmed
    ..In addition to its association with amyloid, ACT immunoreactivity was also located in astrocytes near areas of neuronal or tissue loss, in a few neurons and pericytes and in the epithelium of the choroid plexus. ..
  5. Yamamura J, Miyoshi Y, Tamaki Y, Taguchi T, Iwao K, Monden M, et al. mRNA expression level of estrogen-inducible gene, alpha 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers. Cancer Sci. 2004;95:887-92 pubmed
  6. Qiu Z, Naten D, Liston J, Yess J, Rebeck G. A novel approach for studying endogenous abeta processing using cultured primary neurons isolated from APP transgenic mice. Exp Neurol. 2001;170:186-94 pubmed
  7. Rousham E, Northrop Clewes C, Lunn P. Maternal reports of child illness and the biochemical status of the child: the use of morbidity interviews in rural Bangladesh. Br J Nutr. 1998;80:451-6 pubmed
    ..05). These highly significant associations between maternal reports of illness and biochemical profiles of child health support the use of health interviews in developing countries. ..
  8. Fiebich B, Hofer T, Lieb K, Huell M, Butcher R, Schumann G, et al. The non-steroidal anti-inflammatory drug tepoxalin inhibits interleukin-6 and alpha1-anti-chymotrypsin synthesis in astrocytes by preventing degradation of IkappaB-alpha. Neuropharmacology. 1999;38:1325-33 pubmed
  9. Poller W, Faber J, Scholz S, Weidinger S, Bartholome K, Olek K, et al. Mis-sense mutation of alpha 1-antichymotrypsin gene associated with chronic lung disease. Lancet. 1992;339:1538 pubmed
  10. Bellanger L, Andres C, Seguin P. Epitope mapping of 53 antibodies against prostate-specific antigen. Tumour Biol. 1999;20 Suppl 1:18-23 pubmed
    ..Antibodies with lower affinity for the complex than for the free PSA appeared to bind epitopes in a common region, and thus it was not possible to perform sandwich assays with antibodies specific for free PSA. ..
  11. Wang T, Linton H, Payne J, Rittenhouse H, Chan D, Partin A, et al. Generation of PSA-ACT-specific monoclonal antibodies and their application in a sandwich immunoassay. Hybridoma. 1999;18:535-41 pubmed
    ..Complex PSA by itself or as ratio with free or total PSA does not provide any advantage over the established method of FPSA to total PSA ratio. ..
  12. Vercaigne Marko D, Carrere J, Ducourouble M, Davril M, Laine A, Amouric M, et al. "In vivo" and "in vitro" inhibition of human pancreatic chymotrypsin A by serum inhibitors. Biol Chem Hoppe Seyler. 1987;368:37-45 pubmed
    ..In acute pancreatitis, the chymotrypsin A plasma level follows the progression of the disease and in this case as well as in normal serum alpha 1-PI is the major antagonist of chymotrypsin A. ..
  13. Lindmark B, Lilja H, Alm R, Eriksson S. The microheterogeneity of desialylated alpha 1-antichymotrypsin: the occurrence of two amino-terminal isoforms, one lacking a His-Pro dipeptide. Biochim Biophys Acta. 1989;997:90-5 pubmed
    ..Although the occurrence of heterozygous familial ACT deficiency implies genotypic variation, isolated ACT from patients with the trait was not found to exhibit any phenotypic variation detectable by standard electrophoretic methods. ..
  14. Yonou H, Horiguchi Y, Ohno Y, Namiki K, Yoshioka K, Ohori M, et al. Prostate-specific antigen stimulates osteoprotegerin production and inhibits receptor activator of nuclear factor-kappaB ligand expression by human osteoblasts. Prostate. 2007;67:840-8 pubmed
  15. Consolandi C, Severgnini M, Frosini A, Caramenti G, De Fazio M, Ferrara F, et al. Polymerase chain reaction of 2-kb cyanobacterial gene and human anti-alpha1-chymotrypsin gene from genomic DNA on the In-Check single-use microfabricated silicon chip. Anal Biochem. 2006;353:191-7 pubmed
    ..These thermal cycling characteristics suggest that the In-Check device will permit future development of a genotyping lab-on-a-chip device, yielding results in a short time from a limited amount of biological starting material. ..
  16. Hara I, Miyake H, Hara S, Yamanaka N, Ono Y, Eto H, et al. Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and its density as a predictor for the extent of prostate cancer. BJU Int. 2001;88:53-7 pubmed
    ..Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD. ..
  17. Hara I, Miyake H, Hara S, Yamada Y, Takechi Y, Fujisawa M, et al. Significance of prostate-specific antigen--alpha(1)-antichymotrypsin complex for diagnosis and staging of prostate cancer. Jpn J Clin Oncol. 2001;31:506-9 pubmed
  18. Korzus E, Luisetti M, Travis J. Interactions of alpha-1-antichymotrypsin, alpha-1-proteinase inhibitor, and alpha-2-macroglobulin with the fungal enzyme, seaprose. Biol Chem Hoppe Seyler. 1994;375:335-41 pubmed
  19. Skrzydewska E, Stankiewicz A, Michalak K, Sulkowska M, Zalewski B, Piotrowski Z. Antioxidant status and proteolytic-antiproteolytic balance in colorectal cancer. Folia Histochem Cytobiol. 2001;39 Suppl 2:98-9 pubmed
    ..Activity of alpha-2-macroglobulin was decreased and activity of determined enzymes was not significantly changed. The observed changes indicate a shift in proteolytic-antiproteolytic balance which may enhance carcinogenesis. ..
  20. Schuhmann M, Zucht H, Nassimi R, Heine G, Schneekloth C, Stuerenburg H, et al. Peptide screening of cerebrospinal fluid in patients with glioblastoma multiforme. Eur J Surg Oncol. 2010;36:201-7 pubmed publisher
    ..With regard to GBM, however, the more important role of CSF peptide biomarkers than aiding initial diagnosis might be early recognition of disease recurrence or monitoring of efficacy of adjuvant therapy protocols. ..
  21. Scacchi R, Ruggeri M, Gambina G, Martini M, Ferrari G, Corbo R. Plasma alpha1-antichymotrypsin in Alzheimer's disease; relationships with APOE genotypes. Neurobiol Aging. 2001;22:413-6 pubmed
    ..67). Taken together our results seem to suggest that inflammation is a relevant factor in AD pathogenesis for subjects with E3-E3 and E3-E2 genotypes but less important for APOE*4 carrying subjects. ..
  22. Wan J, Sun W, Li X, Ying W, Dai J, Kuai X, et al. Inflammation inhibitors were remarkably up-regulated in plasma of severe acute respiratory syndrome patients at progressive phase. Proteomics. 2006;6:2886-94 pubmed
  23. Wang J, Zhao C, Si Y, Liu Z, Chen B, Yu L. ACT and UCH-L1 polymorphisms in Parkinson's disease and age of onset. Mov Disord. 2002;17:767-71 pubmed
    ..557 (95% C.I. = 0.314-0.985; P = 0.043). These data suggest that ACT polymorphism does not influence the risk for developing PD. UCH-L1 S18Y polymorphism, however, may be a weak protective factor against early-onset PD. ..
  24. Kim K, Jhoo J, Lee K, Lee D, Lee J, Youn J, et al. No association between presenilin 1 (PS1) intronic polymorphism and sporadic Alzheimer's disease in Koreans. J Neural Transm (Vienna). 2000;107:1191-200 pubmed
    ..02, df = 2, P > 0.1). In conclusion, the PS1 intronic polymorphism did not modify the risk for sporadic AD, neither independently nor synergistically with the APOE epsilon4 allele or ACT A allele, in Koreans. ..
  25. Kiss D, Xu W, Gopalan S, Buzanowska K, Wilczynska K, Rydel R, et al. Duration of alpha 1-antichymotrypsin gene activation by interleukin-1 is determined by efficiency of inhibitor of nuclear factor kappa B alpha resynthesis in primary human astrocytes. J Neurochem. 2005;92:730-8 pubmed
    ..We propose that the tissue-specific regulation of the ACT gene expression by IL-1 is determined by different efficiencies of IkBalpha resynthesis in glial and hepatic cells. ..
  26. Christensson A, Laurell C, Lilja H. Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur J Biochem. 1990;194:755-63 pubmed
    ..This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo. ..
  27. Miller J, Zhou H, Kwekel J, Cavallo R, Burke J, Butler E, et al. Antibody microarray profiling of human prostate cancer sera: antibody screening and identification of potential biomarkers. Proteomics. 2003;3:56-63 pubmed
    ..These developments enable the immediate use of high-density antibody and protein microarrays in biomarker discovery studies. ..
  28. Benchabane M, Saint Jore Dupas C, Faye L, Gomord V, Michaud D. Nucleocytoplasmic transit of human alpha1-antichymotrypsin in tobacco leaf epidermal cells. Plant Biotechnol J. 2009;7:161-71 pubmed publisher
  29. Boudier C, Bousquet J, Schauinger S, Michels B, Bieth J. Reversible inactivation of serpins at acidic pH. Arch Biochem Biophys. 2007;466:155-63 pubmed
  30. Stefansson S, Yepes M, Gorlatova N, Day D, Moore E, Zabaleta A, et al. Mutants of plasminogen activator inhibitor-1 designed to inhibit neutrophil elastase and cathepsin G are more effective in vivo than their endogenous inhibitors. J Biol Chem. 2004;279:29981-7 pubmed
    ..Finally, the PAI-1 mutants were more effective in reducing the neutrophil elastase and cathepsin G activities in an in vivo model of lung inflammation than were their physiological inhibitors. ..
  31. Pearce M, Cabrita L, Rubin H, Gore M, Bottomley S. Identification of residual structure within denatured antichymotrypsin: implications for serpin folding and misfolding. Biochem Biophys Res Commun. 2004;324:729-35 pubmed
    ..The implications of these data on the folding and misfolding of the serpin superfamily are discussed. ..
  32. Range N, Malenganisho W, Temu M, Changalucha J, Magnussen P, Krarup H, et al. Body composition of HIV-positive patients with pulmonary tuberculosis: a cross-sectional study in Mwanza, Tanzania. Ann Trop Med Parasitol. 2010;104:81-90 pubmed publisher
    ..There is need for a better understanding of the determinants and effects of loss of fat and lean body mass in HIV-positive tuberculosis. ..
  33. Benchabane M, Saint Jore Dupas C, Bardor M, Faye L, Michaud D, Gomord V. Targeting and post-translational processing of human alpha1-antichymotrypsin in BY-2 tobacco cultured cells. Plant Biotechnol J. 2009;7:146-60 pubmed publisher
    ..Studies are now needed to assess the activity of the different AACT variants, and to identify the molecular determinants for the nuclear localization of AACT expressed in the cytosol. ..
  34. Martínez Sarmiento M, Espana F, Royo M, Estelles A, Aznar J, Peinado F, et al. [Factors affecting the PSA:alpha 1 antichymotrypsin/total PSA ratio]. Actas Urol Esp. 2001;25:350-6 pubmed
    ..The C/T ratio is independent of age, prostate volume, Gleason and clinical stage. Therefore, these factors need not to be considered when using the C/T ratio. ..
  35. Balercia G, Bhan A, Dickersin G. Sarcomatoid carcinoma: an ultrastructural study with light microscopic and immunohistochemical correlation of 10 cases from various anatomic sites. Ultrastruct Pathol. 1995;19:249-63 pubmed
  36. Sun Y, Wright H, Janciauskiene S. Glioma cell activation by Alzheimer's peptide Abeta1-42, alpha1-antichymotrypsin, and their mixture. Cell Mol Life Sci. 2002;59:1734-43 pubmed
    ..These data suggest a possible new role for Abeta in Alzheimer's disease through its interaction with the inflammatory reactant, ACT. ..
  37. Mikolajczyk S, Marks L, Partin A, Rittenhouse H. Free prostate-specific antigen in serum is becoming more complex. Urology. 2002;59:797-802 pubmed
  38. Miyake H, Hara S, Nomi M, Arakawa S, Kamidono S, Hara I. Value of prostate specific antigen alpha1-antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL: comparison with PSA-related parameters. Int J Urol. 2001;8:589-93 pubmed
  39. Ritchie A, Morgan K, Kalsheker N. Allele-specific overexpression in astrocytes of an Alzheimer's disease associated alpha-1-antichymotrypsin promoter polymorphism. Brain Res Mol Brain Res. 2004;131:88-92 pubmed
  40. Martínez Sarmiento M, Espana F, Royo M, Estelles A, Aznar J, Vera Donoso C, et al. [PSA:alpha 1-antichymotrypsin ratio/total PSA in the diagnosis of prostatic cancer in the range of total PSA from 4 to 10 ng/ml]. Actas Urol Esp. 2001;25:269-77 pubmed
    ..Moreover, the rectal examination does not influence the selection of ratio C/T cut-off suggestives of CaP neither the diagnostic efficacy. ..
  41. Licastro F, Pedrini S, Caputo L, Annoni G, Davis L, Ferri C, et al. Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?. J Neuroimmunol. 2000;103:97-102 pubmed
    ..Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD. ..
  42. Huttunen M, Harvima I. Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially destructive to epithelium and is controlled by proteinase inhibitors. Br J Dermatol. 2005;152:1149-60 pubmed
    ..Even though chymase is partially inactivated in chronic leg ulcers, accumulated mast cells in the close proximity of the epithelium edge and their chymase may impair keratinocyte adherence and migration. ..
  43. Duranton J, Adam C, Bieth J. Kinetic mechanism of the inhibition of cathepsin G by alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor. Biochemistry. 1998;37:11239-45 pubmed
    ..Such an in vivo inhibition mechanism might take place with other serpin/proteinase systems. ..
  44. O Riordan E, Orlova T, Podust V, Chander P, Yanagi S, Nakazato M, et al. Characterization of urinary peptide biomarkers of acute rejection in renal allografts. Am J Transplant. 2007;7:930-40 pubmed
    ..In conclusion, the ratio of beta-Defensin-1 and alpha-1-antichymotrypsin excretion in the urine is a novel, potentially useful candidate biomarkers of acute rejection. ..
  45. Laine A, Hachulla E, Hayem A. The microheterogeneity of serum alpha 1-antichymotrypsin revealed by interaction with concanavalin A in crossed immunoaffinoelectrophoresis and in affinity chromatography. Electrophoresis. 1989;10:227-33 pubmed
    ..This approach represents a first step towards the elucidation of the molecular basis of the microheterogeneity of alpha 1-antichymotrypsin. ..
  46. Manolov T, Forsgren A, Riesbeck K. Purification of alpha1-antichymotrypsin from human plasma with recombinant M. catarrhalis ubiquitous surface protein A1. J Immunol Methods. 2008;333:180-5 pubmed publisher
    ..catarrhalis and a chymotrypsin inhibition assay. The novel method for ACT isolation from plasma has important advantages in simplicity and time as compared to conventional methods. ..
  47. Braghin E, Galimberti D, Scarpini E, Bresolin N, Baron P. Alpha1-antichymotrypsin induces TNF-alpha production and NF-kappaB activation in the murine N9 microglial cell line. Neurosci Lett. 2009;467:40-2 pubmed publisher
    ..Furthermore, we show that ACT induces a significant increase in NF-kappaB nuclear translocation. Taken together, these data demonstrate that ACT might contribute to the inflammatory mechanisms present in AD senile plaques. ..
  48. Retz W, Thome J, Durany N, Harsanyi A, Retz Junginger P, Kornhuber J, et al. Potential genetic markers of sporadic Alzheimer's dementia. Psychiatr Genet. 2001;11:115-22 pubmed
    ..We conclude that, apart from the ApoE allele 4, other genetically regulated factors like ApoCI and the LDL receptor modulate the individual risk for Alzheimer's disease. ..
  49. Mallya M, Phillips R, Saldanha S, Gooptu B, Brown S, Termine D, et al. Small molecules block the polymerization of Z alpha1-antitrypsin and increase the clearance of intracellular aggregates. J Med Chem. 2007;50:5357-63 pubmed
    ..Identifying small molecules provides a novel therapy for the treatment of liver disease associated with the Z allele of alpha1-antitrypsin. ..
  50. Hak A, Pols H, Stehouwer C, Meijer J, Kiliaan A, Hofman A, et al. Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study. J Clin Endocrinol Metab. 2001;86:4398-405 pubmed
    ..These factors may contribute to the well-known relationship between insulin resistance and cardiovascular disease risk and might potentially become therapeutic targets in insulin resistant subjects. ..
  51. Jung K, Lein M, Brux B, Sinha P, Schnorr D, Loening S. Different stability of free and complexed prostate-specific antigen in serum in relation to specimen handling and storage conditions. Clin Chem Lab Med. 2000;38:1271-5 pubmed
  52. Hill R, Shaw P, Boyd P, Baumann H, Hastie N. Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions. Nature. 1984;311:175-7 pubmed
    ..We propose that the genes for contrapsin and human alpha 1-antichymotrypsin are the descendents of a single gene that have evolved since rodent and primate divergence to encode proteins with different functions. ..
  53. Laursen I, Lykkesfeldt A. Purification and characterization of an alpha 1-antichymotrypsin-like 66 kDa protein from the human breast cancer cell line, MCF-7. Biochim Biophys Acta. 1992;1121:119-29 pubmed
    ..The results of our growth experiments suggest that the 66 kDa protein is a minor positive growth regulatory factor, which may contribute to breast carcinoma cell proliferation in a cooperative manner. ..