Protein alpha -antitrypsin

G7. Gross, V., Scholmerich, J., Leser, H. G., Salm, R., Lausen, M., and Ruckauer, K., Granulocyte elastase in assessment of severity of acute pancreatitis. Comparison with acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and protease inhibitor alpha 2-macroglobulin. Dig. Dis. Sci. 35, 97-105 (1990). 

Filie AC, Lage JM, Azumi N. Immunoreactivity of SlOO protein, alpha-1-antitrypsin, and CD68 in adult and congenital granular cell tumors. Mod Pathol. 1996 9 888-892. 

PPL Therapeutics Bile human gastric Lipase, Fibrinogen, thrombin, Factor VII, Factor IX, alpha-antitrypsin, calcitonin (salmon), collagen, superoxide dismutase, Glucagon lipopeptide, Human serum albumin, Protein C 59-63... 

Emphysema is caused by smoking cigarettes, by inhaling contaminants from the environment, or by the lack of the alpha -antitrypsin protein. The lung contains bacteria that release proteol5dic enzymes that destroy alveoli. The alphaj-antitrypsin protein inhibits proteolytic enzymes and protects the alveoli. 

H. Galeazzi, L. Xhe inflammation-sensitive protein alpha 1-anti-chymotrypsin neutralizes fibrillar aggregation and cytotoxicity of the beta-amyloid peptide more effectively than alpha 1-antitrypsin. Clin. Biochem. 2007, 40, 887-892. 

Griffiths S.W. and Cooney C.L. (2002), Relationship between protein structure and methionine oxidation in recombinant human alpha 1-antitrypsin, Biochemistry 41, 6245-6252. 

Alpha-1 antitrypsin deficiency Cardiovascular diseases Familial hypercholesterolemia Many types using vaccine, toxin or endogenous regulatory protein expression strategies... 

Hidvegi, T, Schmidt, B.Z., Hale, P. andPerlmutter, D.H. (2005) Accumulation ofmutant alpha 1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response. J. Biol. Chem. 280, 39002-39015. 

Alpha-1-antitrypsin mutations are associated with early-onset emphysema and liver disease that results in early death (50). The Z-variant of the disease is the most common and is present in over 95% of cases. This variant has been shown to be rescued in vitro by treatment with proteasome inhibitors (50). Several chemical and pharmacological chaperones have also been shown to correct the secretion of the mutant protein, which include the glucosidase inhibitor castanospermine, as well as the mannosidase inhibitors kifunensine (Fig. 2b)... 

Another common mechanism of correction is ER glucosidase inhibition (Fig. 1, star 2), which prevents the recognition of misfolded proteins by calnexin and calreticulin and presumably allows them to escape the ERQC. Inhibition of glucosidase with castanospermine and miglustat were shown to correct the trafficking of deltaE508 CFTR and alpha-l-antitrypsin (51, 61). Whether this mechanism also works on other ER-retained mutants remains to be determined. 

Perlmutter, D.H. Liver injury in alpha(l)-antitrypsin deficiency an aggregated protein induces mitochondrial injury (review). J. Clin. Invest. 2002 110 1579-1583... 

Hubbard, R.C. Alpha-1 antitrypsin. In Inhalation Delivery of Therapeutic Peptides and Proteins Adjei, A.L., Gupta, P.R., Eds. Marcel Dekker, Inc. New York, 1997 315-330, Ch. 10. 

The combination of MALDI-TOF MS and capillary LC/MS/MS was recently described for the identification of disease state markers in human urine. In this study, urine proteins obtained from emphysema patients were separated on 2-D gels and selected spots were digested with trypsin and analyzed by MALDI-TOF. A database search using Protein Prospector identified a potential biomarker for emphysema as human alpha-1-antitrypsin (AlAT). The corresponding MALDI spectrum contained nine out of 18 peptides with masses that match the expected tryptic digest fragments for AlAT. 

Penicillamine can cause an artificially abnormal alpha-1 antitrypsin protein pattern, which can result in diagnostic errors (404). 

The fecal clearance of alpha-1-antitrypsin (AT) can also be used as a marker of GI protein loss. AT is a glycoprotein (MW 54,000) that is synthesized in the fiver and is normally present in the serum at a concentration of about 1.5 to 2 g/L. It is a protease inhibitor and therefore resistant to degradation by proteolytic enzymes in the GI tract. The fecal clearance of AT correlates with protein loss measured by Cr techniques (r = 0.96). The correlation is not influenced by serum AT concentrations or by fecal weight. AT clearance can be used for both small and large bowel disease and is appficable to the evaluation of enteric protein loss in children or adults.More recent work has confirmed these findings and also confirmed that fecal AT concentration alone does not reliably predict AT clearance (i.e., a timed fecal sample and measurement of serum AT is required). An important observation is that experimentally induced diarrhea in normal subjects leads to an increased AT clear-... 

Eng B, et al. Fecal clearance of alpha-1-antitrypsin a reliable measure of enteric protein loss in cMdren. 

The granular cell tumor (GCT) is an uncommon tumor of Schwann cell origin with a predilection for skin and mucosal surfaces, especially the tongue. Most are benign, but a few are malignant. The tumor is positive for S-100 protein, neuron specific enolase, alpha-l-antitrypsin, CD 68, vimentin, inhibin-alpha, protein gene product... 

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