Hepatic alpha 1-antitrypsin mRNA content in cirrhosis with normal and abnormal protease inhibitor phenotypes.

Hepatic alpha 1-antitrypsin mRNA content in cirrhosis with normal and abnormal protease inhibitor phenotypes.
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具有正常和异常蛋白酶抑制剂表型的肝硬化中肝 α1-抗胰蛋白酶 mRNA 含量。

DOI:
10.1002/hep.1840060605
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发表时间:
1986
期刊:
Hepatology (Baltimore, Md.)
影响因子:
--
通讯作者:
Seelig,S
Seelig,S
中科院分区:
--
文献类型:
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作者:
Schwarzenberg,SJ;Sharp,HL;Manthei,RD;Seelig,S

文献摘要

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我们使用总肝 RNA 和 RNA/DNA 杂交的 [35S] 蛋氨酸标记的翻译产物的二维电泳图定量了正常、α1-抗胰蛋白酶缺乏的肝硬化和胆汁性肝硬化肝脏中的 α1-抗胰蛋白酶 mRNA。通过免疫沉淀法鉴定α1-抗胰蛋白酶前体产物。正常(0.989±0.197)、肝硬化(0.956±0.062)和α1-抗胰蛋白酶缺陷(0.818±0.12)肝脏中α1-抗胰蛋白酶产物的相对丰度没有显着差异。尽管与正常相比,PiZZ 肝硬化肝脏中的 (RNA/DNA) 有所减少(0.56 ± 0.045 与 0.95 ± 0.225),但与 PiM 肝硬化肝脏中的结果相同(0.56 ± 0.055)。尽管与正常肝脏相比,PiZZ 中的 α1-抗胰蛋白酶 mRNA 浓度 [相对丰度 × (RNA/DNA)] 降低,但 PiZZ 肝硬化患者与 PiM 肝硬化患者没有差异。我们使用 α1-抗胰蛋白酶基因组探针对 α1-抗胰蛋白酶 mRNA 进行定量,证实了这一观察结果。通过 RNA/DNA 杂交,PiM 肝硬化和 PiZZ 肝硬化中的 α1-抗胰蛋白酶 mRNA 相等(38.48 ± 4.5 vs. 31.93 ± 2.1),但与非肝硬化 PiM 肝脏相比显着降低(58.36 ± 12.7)。我们得出的结论是,在任何病因的肝硬化中,α1-抗胰蛋白酶 mRNA 都会减少,这种减少似乎代表了肝脏对损伤的一般反应。由于 PiM 肝硬化中 α1-抗胰蛋白酶 mRNA 的降低与正常血清 α1-抗胰蛋白酶水平相关,因此 PiZZ 肝硬化中 α1-抗胰蛋白酶 mRNA 的降低不太可能解释其血清水平的降低。
We quantitated α1‐antitrypsin mRNA in normal, α1‐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. α1‐antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of α1‐antitrypsin product from normal (0.989 ± 0.197), cirrhotic (0.956 ± 0.062) and α1‐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 α1‐antitrypsin mRNA [relative abundance × (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 α1‐antitrypsin mRNA using an α1‐antitrypsin genomic probe. By RNA/DNA hybridization, α1‐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 α1‐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 α1‐antitrypsin mRNA in PiM cirrhotics is associated with normal serum α1‐antitrypsin levels, it is unlikely that the decreased α1‐antitrypsin mRNA in PiZZ cirrhotics accounts for their decreased serum levels.