Hepatic α1-antitrypsin mRNA content in cirrhosis with normal and abnormal protease inhibitor phenotypes
✍ Scribed by Dr. Sarah Jane Schwarzenberg; Harvey L. Sharp; Robin D. Manthei; Dr. Steven Seelig
- Book ID
- 102852180
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 814 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
We quantitated al-antitrypsin mRNA in normal, alantitrypsin-deficient cirrhotic and biliary cirrhotic livers using two-dimensional electrophoretograms of [36S] methionine-labeled translational products of total hepatic RNA and RNA/DNA hybridization. al-Antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of al-antitrypsin product from normal (0.989 f 0.197), cirrhotic (0.956 f 0.062) and al-antitrypsin deficient (0.818 f 0.12) livers was not significantly different. Although (RNADNA) was decreased in the PiZZ cirrhotic livers compared to normal (0.56 f 0.045 vs. 0.95 f 0.225), it equaled that found in the PiM cirrhotic livers (0.56 f 0.055). The concentration of al-antitrypsin mRNA [relative abundance X (RNADNA)], while decreased in PiZZ compared to normal liver, is thus no different in PiZZ cirrhotics than in PiM cirrhotics. We confirmed this observation by quantitation of the al -antitrypsin mRNA using an al-antitrypsin genomic probe. By RNADNA hybridization, al-antitrypsin mRNA was equal in PiM cirrhotic and PiZZ cirrhotic (38.48 2 4.5 vs. 31.93 f 2.1), but significantly decreased from noncirrhotic PiM liver (58.36 f 12.7). We conclude that al-antitrypsin mRNA is decreased in cirrhosis of any etiology, and this decrease appears to represent a general response of the liver to injury. Since the decreased al-antitrypsin mRNA in PiM cirrhotics is associated with normal serum al-antitrypsin levels, it is unlikely that the decreased al-antitrypsin mRNA in PiZZ cirrhotics accounts for their decreased serum levels. al-Antitrypsin is a polymorphic glycoprotein produced predominantly by the hepatocyte and controlled by codominant alleles (1). Deficiency of this antiprotease is associated with childhood liver disease and predisposes young adults to emphysema. In the genetic variant most commonly associated with disease (designated protease inhibitor Z or PiZ), lysine is substituted for glutamic acid at position 342 in the polypeptide chain (2).