Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasio...Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.展开更多
目的观察α1抗胰蛋白酶(α1-antitrypsin,AAT)Z型突变体(α1-antitrypsin Z variant,ATZ)表达对细胞自噬水平的影响,探讨ATZ细胞毒作用的可能机制。方法体外培养人胚肾细胞株HEK 293T并转染ATZ真核表达质粒,利用Western blot法检测自噬...目的观察α1抗胰蛋白酶(α1-antitrypsin,AAT)Z型突变体(α1-antitrypsin Z variant,ATZ)表达对细胞自噬水平的影响,探讨ATZ细胞毒作用的可能机制。方法体外培养人胚肾细胞株HEK 293T并转染ATZ真核表达质粒,利用Western blot法检测自噬相关蛋白LC3和p62的表达,免疫荧光染色观察LC3的细胞定位,real-time PCR法检测自噬相关基因Atg5、Atg12和Beclin1的变化,DAB染色观察ATZ过表达对细胞形态的影响。结果与转染空质粒对照组相比,ATZ过表达促进细胞自噬的标志分子LC3由LC3-Ⅰ转变为LC3-Ⅱ,p62水平降低;而经自噬抑制剂氯化铵处理后,ATZ过表达细胞中出现LC3点状聚集,p62水平增加;同时,ATZ过表达明显增加自噬相关基因Atg5、Atg12的mRNA水平,而对Beclin1无明显影响;少量表达ATZ的细胞形态基本正常,细胞中LC3形成点状聚集;反之,过度表达ATZ的细胞核变小、固缩甚至消失,无LC3-Ⅱ表达。结论过表达ATZ通过增加Atg5和Atg12表达激活自噬,这可能与其细胞毒性有一定相关性。展开更多
Ⅰ. INTRODUCTION Alpha-1-antitrypsin (A1AT; locus symbol, PI) is one of the main protease inhibitors in serum. Up to now there are at least 50 A1AT variants that have been found in human populations (Cox, D. W., priva...Ⅰ. INTRODUCTION Alpha-1-antitrypsin (A1AT; locus symbol, PI) is one of the main protease inhibitors in serum. Up to now there are at least 50 A1AT variants that have been found in human populations (Cox, D. W., private communication). The distribution of A1AT variants appears highly racial specificity and geographical variability. This展开更多
基金Supported by The Borsa M.Coppo AISF,Italian Association for the Study of the Liver to Rametta R
文摘Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.
基金Project supported by the Science Fund of Academia Sinica
文摘Ⅰ. INTRODUCTION Alpha-1-antitrypsin (A1AT; locus symbol, PI) is one of the main protease inhibitors in serum. Up to now there are at least 50 A1AT variants that have been found in human populations (Cox, D. W., private communication). The distribution of A1AT variants appears highly racial specificity and geographical variability. This
