Hepatic alpha 1-antitrypsin mRNA content in cirrhosis with normal and abnormal protease inhibitor phenotypes.
We quantitated alpha 1-antitrypsin mRNA in normal, alpha 1-antitrypsin-deficient cirrhotic and biliary cirrhotic livers using two-dimensional electrophoretograms of [35S]methionine-labeled translational products of total hepatic RNA and RNA/DNA hybridization. alpha 1-Antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of alpha 1-antitrypsin product from normal (0.989 +/- 0.197), cirrhotic (0.956 +/- 0.062) and alpha 1-antitrypsin deficient (0.818 +/- 0.12) livers was not significantly different. Although (RNA/DNA) was decreased in the PiZZ cirrhotic livers compared to normal (0.56 +/- 0.045 vs. 0.95 +/- 0.225), it equaled that found in the PiM cirrhotic livers (0.56 +/- 0.055). The concentration of alpha 1-antitrypsin mRNA [relative abundance X (RNA/DNA)], 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 alpha 1-antitrypsin mRNA using an alpha 1-antitrypsin genomic probe. By RNA/DNA hybridization, alpha 1-antitrypsin mRNA was equal in PiM cirrhotic and PiZZ cirrhotic (38.48 +/- 4.5 vs. 31.93 +/- 2.1), but significantly decreased from noncirrhotic PiM liver (58.36 +/- 12.7). We conclude that alpha 1-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 alpha 1-antitrypsin mRNA in PiM cirrhotics is associated with normal serum alpha 1-antitrypsin levels, it is unlikely that the decreased alpha 1-antitrypsin mRNA in PiZZ cirrhotics accounts for their decreased serum levels.
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D007223:Infant; D008099:Liver / Q000032:analysis*; D008103:Liver Cirrhosis / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis*; D000515:alpha 1-Antitrypsin / Q000032:analysis*
D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D012313:RNA; D004247:DNA