Al-antitrypsin

Yeast expression vectors have been among those most commonly used since the beginning of gene technology. Vectors based on baker s yeast, Saccharomyces cerevisiae, have been especially popular for robust expression of many types of recombinant proteins [90]. For instance, the first commercially available recombinant vaccine, the hepatitis B surface antigen vaccine, was produced from an S. cerevisiae vector [91]. Many other recombinant proteins have also been efficiently expressed in yeast including al-Antitrypsin [92], insulin [93], Epstein-Barr virus envelope protein [94], superoxide dismutase [95] and interferon-a [90]. 

Another serine protease inhibitor of the al-antitrypsin family (serpin) is heparin cofactor II (HCII), which also forms a 1 1 complex with thrombin, but does not react with factor Xa [4,10]. The rate of inhibition of thrombin is not only increased by heparinoids but also by the related glycosaminoglycan dermatan sulfate. The identification of an inhibitor variant and site-directed mutagenesis studies on HC II cDNA led to the understanding that the binding sites for heparin and dermatan sulfate may be overlapping but not identical. Further proteinase inhibitors interacting with heparinoids are tissue factor pathway inhibitor and protease nexin-1. 

De, B., A. Heguy, P.L. Leopold, N. Wasif, R.J. Korst, N.R. Hackett, and R.G. Crystal. 2004. Intrapleural administration of a serotype 5 adeno-associated virus coding for al-antitrypsin mediates persistent, high... 

Post-separation labeling was also achieved for separation of four human serum proteins (IgG, transferrin, al-antitrypsin, and albumin) using 0.2 mM of TNS. This is a virtually non-fluorescent reagent which, upon non-covalent association with proteins, produces a fluorescent complex (A= 325 nm, A = 450... 

Figure 6 Oxidative stress in COPD. Oxidative stress plays a key role In the pathophysiology of COPD and amplifies the inflammatory and destructive process. ROS from cigarette smoke or from inflammatory cells (particularly macrophages and neutrophils) result in several damaging effects in COPD, which include decreased antiprotease defenses, such as al -antitrypsin (AD and secretory leukoprotease inhibitor (SLPI), activation of NF-kB resulting in increased secretion of the cytokines CXCL8 and TNF-as, increased production of isoprostanes, and direct effects on airway function. In addition, recent evidence suggests that oxidative stress induces steroid resistance.

Pauluhn, J. Martins, T. Effects and Eate of Aerosolized al-Antitrypsin (al-AT) in Rats Following Subacute Inhalation Exposure, Abstracts of Fourth International Aerosol Conference, Los Angeles, CA, Aug 24—Sep 2, 1994. 

Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol 1992 38(Suppl 1) S20-S27. Tencer J,Thysell H, Grubb A. Analysis of proteinuria Reference limits for urine excretion of albumin, protein HC, immunoglobin G, k- and 1-chain immunoreactrivity, orosomucoid and al-antitrypsin. Scand J Clin Lab invest 1996 56 691-700. 

Lomas DA, Elliott PR> Sidhar SK, Foreman RC> Finch JT, Cox DW, et al. al-Antitrypsin Mmalton (Phe52-deleted) forms loop-sheet polymers in vivo Evidence for the C sheet mechanism of polymerization. J Biol Chem 1995 270 16864-70. 

Expression of recombinant proteins in the milk of transgenic animals is gaining popularity due to simple and cost effective production. Over the past several years, the feasibility of this approach has been demonstrated by the production, at mg mb1 levels, of pharmaceutically relevant monomeric proteins such as human al -antitrypsin, human tPA, human protein C and hexameric fibrinogen [166]. However there are limitations of mammary tissue in making the meaningful post-translational modifications, which has been overcome by co expression of key pro cessing enzymes [167]. 

Human al-antitrypsin 100mg/L Rice suspension culture [25] ... 

Carrell RW, Travis J. al-Antitrypsin and the serpins Variation and countervariation. Trends Biochem Sci 1985 10 20-24. 

Figure 6.8 Linear mode MALDI spectra of native N-glycans obtained by in-gel PNCase F digestion from the 2-D gel of al-antitrypsin spots of a CDC-type-llx patient in the...

Bierwolf et al. (2012) seeded primary human hepatocytes isolated from the liver of metabolic-disordered children to recreate differentiated liver tissue-like spheroids on alginate MCs. Formation of hepatocyte spheroids was detected from day 3, and excellent metabolic functions of albumin, al-antitrypsin, and urea were obtained with their maximum at day 7. Furthermore, highly differentiated hepatocytes in spheroids with a tissue-like structure on the alginate MCs was obtained, indicating that alginate MCs provide a favorable microenvironment for hver neo-tissue recreation and regeneration. 

Mice hepatic-layered cell sheets, which express human al-antitrypsin, are transplanted into mice subcutaneous locations with neovascular networks (Ohashi et al., 2007). After transplantation, liver-specific functions such as albumin production and drug metabolism are improved and kept for longer than 200 days. In addition, the transplanted cell sheet has an ability to proliferate and grow in response to a regenerative stimulus, which is induced by the resection of two-thirds of the host liver (Ohashi et al., 2007). 

LDL receptor-related protein/ ff2-macroglobulin receptor (LRP) Apo-E, lipoprotein lipase, hepatic lipase, thrombospondin. Pseudomonas exotoxin A, a2-macroglobulin, receptor-associated protein (RAP), lactofetrin, t-PA, u-PA, t-PA PAl-l, u-PA PAl-l, elastase-al-antitrypsin liver, brain, lung, adrenal, intestine, kidney, placenta, ovary, testis... 

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