ArticlePloS one2018
NorUDCA promotes degradation of α1-antitrypsin mutant Z protein by inducing autophagy through AMPK/ULK1 pathway.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Diverse Forms of Autophagy and Their Roles in Liver Disease and Aging: A Comprehensive Review.Proteomes · 2026Review
- Adaptive Regulation of mTOR Activity by AMPK, Akt, and ATF6 Pathways in Pi*Z Alpha-1 Antitrypsin Deficient Hepatocytes.Biomolecules · 2026Article
- Characterization of a novel SERPINA1 variant carrying two missense mutations: molecular mechanisms and functional impact.Orphanet journal of rare diseases · 2025Article
- Pioglitazone reduces hepatic α-1 antitrypsin accumulation through autophagy and AMPK activation in α-1 antitrypsin-deficient mice.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Alpha-1 Antitrypsin Inclusions Sequester GRP78 in a Bile Acid-Inducible Manner.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- FGF21-mediated autophagy: Remodeling the homeostasis in response to stress in liver diseases.Genes & diseases · 2024Review
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Berberine potentiates liver inflammation and fibrosis in the PI*Z hAAT transgenic murine model.PloS one · 2024Article
- The anticancer activity of bile acids in drug discovery and development.Frontiers in pharmacology · 2024Review
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Alpha-1 antitrypsin Pi∗Z allele is an independent risk factor for liver transplantation and death in patients with advanced chronic liver disease.JHEP reports : innovation in hepatology · 2022Article
- The Interplay between Finasteride-Induced Androgen Imbalance, Endoplasmic Reticulum Stress, Oxidative Stress, and Liver Disorders in Paternal and Filial Generation.Biomedicines · 2022Review
- Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review.International journal of molecular sciences · 2022Review
- Therapeutic regulation of autophagy in hepatic metabolism.Acta pharmaceutica Sinica. B · 2022Review
- Protein Misfolding and Aggregation: The Relatedness between Parkinson's Disease and Hepatic Endoplasmic Reticulum Storage Disorders.International journal of molecular sciences · 2021Review
- Review
- The molecular species responsible for αThe FEBS journal · 2021Article
- Autophagy in liver diseases.World journal of hepatology · 2021Review
- ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets.Frontiers in molecular biosciences · 2021Review
- Alpha-1 Antitrypsin Z Variant (AAT PI*Z) as a Risk Factor for Intrahepatic Cholestasis of Pregnancy.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-1 Antitrypsin (α1AT) Deficiency is a genetic disease in which accumulation of α1AT mutant Z (α1ATZ) protein in the ER of hepatocytes causes chronic liver injury, liver fibrosis, and hepatocellular carcinoma. No effective medical therapy is currently available for the disease. We previously found that norUDCA improves the α1AT deficiency associated liver disease by promoting autophagic degradation of α1ATZ protein in liver in a mouse model of the disease. The current study unravels the novel underlying cellular mechanism by which norUDCA modulates autophagy. HTOZ cells, modified from HeLa Tet-Off cells by transfection with the resulting pTRE1-ATZ plasmid and expressing mutant Z proteins, were studied in these experiments. The role of norUDCA in inducing autophagy, autophagy-mediated degradation of α1ATZ and the role of AMPK in norUDCA-induced autophagy were examined in the current report. NorUDCA promoted disposal of α1ATZ via autophagy-mediated degradation of α1ATZ in HTOZ cells. Activation of AMPK was required for norUDCA-induced autophagy and α1ATZ degradation. Moreover, mTOR/ULK1 was involved in norUDCA-induced AMPK activation and autophagy in HTOZ cells. Our results provide novel mechanistic insights into the therapeutic action of norUDCA in promoting the clearance of α1ATZ in vitro and suggest a novel therapeutic approach for the treatment of α1ATZ deficiency disease and its associated liver diseases.
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