Alpha-1-proteinase inhibitor

Ansari GAS, Gan JC, Barton BK. 1988. Synergistic inactivation of plasma alpha-proteinase inhibitor by aldehydes of cigarette smoke with styrene oxide and 1,2-dichloroethane. Arch Environ Cont Toxicol 17 533-536. 

In particular, excessive proteolysis of elastin by HLE has been implicated in pulmonary emphysema [19]. In this case, the imbalance appears to result from reduced levels of active extracellular alpha,-proteinase inhibitor (a,-PI), the primary plasma inhibitor of HLE. This decrease is caused either by a genetic disorder (PiZZ phenotype individuals) or by reduction in the elastase inhibitory capacity (EIC) of ai-PI due to its oxidative inactivation by tobacco smoke [20]. The detailed evidence supporting the potential role of elastase in the development of emphysema has been extensively reviewed [21] and will not be repeated here. The fact that HLE is also a potent secretagogue [22] may play a role in several disease states, including cystic fibrosis [23], chronic bronchitis [24], and acute respiratory distress syndrome (ARDS) [25]. The mechanism of the secretagogue activity is not known, but, since the HLE-induced secretion can be blocked by specific HLE inhibitors, it appears to require catalytic activity by the enzyme [26]. 

ALPHA-PROTEINASE INHIBITOR (Human) (Alphaj-PI) (Prolastin)... 

Alpha proteinase inhibitor (60 mg/kg IV once weekly), is indicated for chronic replacement of alpha,-antitrypsin in... 

Alpha,-proteinase inhibitor inhibits serine proteases (e.g., neutrophil elastase), which are capable of degrading protein components of the alveolar walls and which are chronically present in the lung. Alpha,-proteinase inhibitor is indicated in chronic augmentation therapy in patients with congenital deficiency if a,-PI with clinically evident emphysema. 

Alpha-1-proteinase inhibitor and antithrombin III are used to treat people with hereditary deficiencies of these proteins. Both can be recovered from Cohn Fraction IV (Table 7) using ion-exchange chromatography (52) and affinity chromatography (197), respectively. Some manufacturers recover antithrombin III directiy from the plasma stream by affinity adsorption (56,198,199). 

Wong, P.S. and Travis, J. (1980). Isolation and properties of oxidised alpha-l-proteinase inhibitor from human rheumatoid synovial fluid. Biochem. Biophys. Res. Commun. 96, 1449-1454. 

Desrochers, P.E. and Weiss, S.J. (1988). Proteolytic inactivation of alpha-l-proteinase inhibitor by a neutrophil metalloproteinase. J. Clin. Invest. 81, 1646-1650. 

Weissbach, H. and Brot, N. (1981). Enzymatic reduction of oxidised alpha-l-proteinase inhibitor restores biological activity. Proc. Natl Acad. Sci. USA, 78, 7483—7486. 

Alpha-1-proteinase inhibitor, 12 147 a-adrenoceptor blockers, antihypertensive agents, 5 155-156t, 157t, 160... 

Inverse Relationship between Protease Inhibitors and Metastatic Ability. All proteases, apart from possibly CD, appear to be controlled by endogenous inhibitors. In theory, therefore, the ability of malignant cells to produce metastasis could depend not only on the levels of the specific protease, but also on the concentration of relevant endogenous inhibitors. Thus, the presence of high levels of protease inhibitors might inhibit metastasis, while low levels of inhibitors might enhance metastasis. An inverse relationship between a number of specific inhibitors and metastatic potential has now been shown. Some examples of this type of relationship include TIMP-1 in Swiss 3T3 cells (K4), cysteine protease inhibitors in mouse melanoma cells (R6), and an alpha-1-proteinase inhibitor in rat mammary carcinomas (N2). Furthermore, a newly described serine protease inhibitor, known as maspin, was found to be expressed less frequently in advanced human breast cancers compared with early cancers (Z2). 

NT034 Cavarra, E., B. Bartalesi, M. Lucattelli, et al. Effects of cigarette smoke in mice with different levels of alpha( 1)-proteinase inhibitor and sensitivity to oxidants. Am J Respir Crit Care Med 2001 164(5) 886-890. 

Clinical pharmacology Alpha-1 antitrypsin deficiency is a chronic, hereditary, usually fatal, autosomal recessive disorder in which a low concentration of alphai-proteinase inhibitor is associated with slowly progressive, severe, panacinar emphysema that most often manifests itself in the third to fourth decades of fife. The pathogenesis of development of emphysema in alpha-1 antitrypsin deficiency is believed to be due to a chronic biochemical imbalance between elastase and alphai-proteinase inhibitor (the principal inhibitor of neutrophil elastase), which is deficient in alpha-1 antitrypsin disease. As a result it is believed that alveolar structures are unprotected from chronic exposure to elastase released from a chronic low-level burden of neutrophils in the lower respiratory tract, resulting in progressive degradation... 

G. Other consideration Alphai-proteinase inhibitor has been designated an orphan product for use as supplementary or replacement therapy for alpha-1 antitrypsin... 

Alpha-l-proteinase inhibitor (human) [FDA] Aphal-antitrypsin [CAS]... 

Mierzwa, S., and Chan, S. K. (1987). Chemical modification of human alpha 1 proteinase inhibitor by tertanitromethane. Structure-function relationship. Biochem.J. 246,37-42. 

Moreno J. J. and Pryor W. A. (1992). Inactivation of alpha 1-proteinase inhibitor by peioxynitrite. Chem. Res. Toxicol. 5 425-431. 

H. Loebcunann, R. Tokuoka, J. Ddsenhofcr, and R. Huber. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. /. Mol Biol, mm (1984). 

A. E, Mat, G. Sel vesen, R P. Schnebli, and V. Kzzo. Evaluation of the rapid plasma elimination of recombinant alpha 1-proteinase inhibitor synthesis of polyethylene glycol conjugates with improved therapeutic potential. /. Lab. din. Med. 116 58 (1990). 

In STZ-diabetic rat livers, the levels of mRNA of 1-gulonolactone oxidase, catalase, and glutathione peroxidase were decreased at 6 weeks, as well as that of plasma alpha 1 proteinase inhibitor 3.562 AA synthesis enzyme and recycling enzyme mRNAs were also decreased, as was the level of AA itself. It seems that the antioxidative defence system had been severely damaged. 

Pratt CW, Swaim MW, Pizzo SV. Inflammatory cells degrade inter-alpha-inhibitor to liberate urinary proteinase inhibitors. J Leukoc Biol 1989 45 1-9. 

Hochstrasser K, Schoenberger OL, Rossmanith I, Wachter E. Kunitz-type proteinase inhibitors derived by limited proteolysis of the inter-alpha-trypsin inhibitor. V. Attachments of carbohydrates in the human urinary trypsin inhibitor isolated by affinity chromatography. Hoppe Seylers Z Physiol Chem 1981 362 1357-1362. 

Owen, M. C., and Carrell, R. W., Alpha-1-proteinase inhibitor. In Human Protein Data (A. Haeberli, ed.). VCH Verlagsgesellschaft mbH, Weinheim, 1992. 

B14. Beatty, K., Bieth, J., and Travis, J., Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin. J. Biol. Chem. 255, 3931-3934 (1980). 

Travis J, Owen M, George P, Carrell R, Rosenberg S, Hallewell RA, Barr PJ. Isolation and properties of recombinant DNA produced variants of human alpha 1-proteinase inhibitor. J. Biol. Chem. 1985 260 4384-1389. 

Alphaparin certoparin sodium, alphai-proteinase inhibitor alpha,-antitrypsin, alpha,-trypsin inhibitor alpha,-antitrypsin. alphaxalone [ban] (alfaxalone [inn.jan]) is a semisynthetic steroid produced from 5a-pregnanetrione by incubating with Saccharomyces cerevisiae. It is a general ANAESTHETIC. It can be used as a compound with alhidolone acetate to enhance solubility. 

Turner, G.A., Goodarzi, M.T. and Thompson, S. (1995) Glycosylation of alpha-1-proteinase inhibitor and haptoglobin in ovarian cancer evidence for two different mechanisms. Glyco-conjugate Journal, 12, 211-218. 

A. D. Gounaris, M. A. Brown, and A. J. Barrett. Human plasma alpha-cysteine proteinase inhibitor. Purification by affinity chromatography, characterization and isolation of an active fragment. Biochem. J. 221 445 (1984). 

D. Johnson and J. Travis. Structural evidence for methionine at the reactive site of human alpha-1-proteinase inhibitor. /. Biol. Chem. 253 7142 (1978). 

D. S. Fletcher, D. G. Osinga, K. M. Hand, P. S. Dellea, B. M. Ashe, R. A. Mumford, P. Davies, W. Hagmann, P. E. Finke, J. B. Doherty, and R. J. Bonney. A comparison of alpha 1-proteinase inhibitor methoxysuccinyl-Ala-Ala-Pro-Val-chloro-methylketone and specific beta-lactam inhibitors in an acute model of human polymorphonuclear leukocyte elastase-induced lung hemorrhage in the hamster. Am. Rev. Respir. Dis. 141 612 (1990). 

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