ArticleBMC cell biology2007
Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmic reticulum stress responses.
Article in BMC cell biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 44 citations in OpenAlex.
- Copper, Iron, Cadmium, and Arsenic, All Generated in the Universe: Elucidating Their Environmental Impact Risk on Human Health Including Clinical Liver Injury.International journal of molecular sciences · 2024Review
- HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.International journal of molecular sciences · 2024Review
- Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.International journal of molecular sciences · 2024Review
- Cytokine and Gene Expression Profiling in Patients with HFE-Associated Hereditary Hemochromatosis according to Genetic Profile.Acta haematologica · 2021Article
- Article
- Autophagy mediated by endoplasmic reticulum stress enhances the caffeine-induced apoptosis of hepatic stellate cells.International journal of molecular medicine · 2017Article
- The hemochromatosis protein HFE 20 years later: An emerging role in antigen presentation and in the immune system.Immunity, inflammation and disease · 2017Review
- The unfolded protein response in fatty liver disease.Seminars in liver disease · 2013Review
- Effect of HFE variants on sphingolipid expression by SH-SY5Y human neuroblastoma cells.Neurochemical research · 2011Article
- Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis.International journal of cancer · 2011Article
- Endoplasmic reticulum stress in liver disease.Journal of hepatology · 2011Review
- ER Stress and Iron Homeostasis: A New Frontier for the UPR.Biochemistry research international · 2011Article
- Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1.Journal of neuroinflammation · 2009Article
- Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency.Biologics : targets & therapy · 2009Article
- The unfolded protein response in hereditary haemochromatosis.Journal of cellular and molecular medicine · 2008Review
- Dissection of endoplasmic reticulum stress signaling in alcoholic and non-alcoholic liver injury.Journal of gastroenterology and hepatology · 2008Review
- Alpha-1 antitrypsin deficiency: a conformational disease associated with lung and liver manifestations.Journal of inherited metabolic disease · 2008Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHereditary Hemochromatosis (HH) is a genetic disease associated with iron overload, in which individuals homozygous for the mutant C282Y HFE associated allele are at risk for the development of a range of disorders particularly liver disease. Conformational diseases are a class of disorders associated with the expression of misfolded protein. HFE C282Y is a mutant protein that does not fold correctly and consequently is retained in the Endoplasmic Reticulum (ER). In this context, we sought to identify ER stress signals associated with mutant C282Y HFE protein expression, which may have a role in the molecular pathogenesis of HH.
resultsVector constructs of Wild type HFE and Mutant C282Y HFE were made and transfected into HEK293 cell lines. We have shown that expression of C282Y HFE protein triggers both an unfolded protein response (UPR), as revealed by the increased GRP78, ATF6 and CHOP expression, and an ER overload response (EOR), as indicated by NF-kappaB activation. Furthermore, C282Y HFE protein induced apoptotic responses associated with activation of ER stress. Inhibition studies demonstrated that tauroursodeoxycholic acid, an endogenous bile acid, downregulates these events. Finally, we found that the co-existence of both C282Y HFE and Z alpha 1-antitrypsin protein (the protein associated with the liver disease of Z alpha 1-antitrypsin deficiency) expression on ER stress responses acted as potential disease modifiers with respect to each other.
conclusionOur novel observations suggest that both the ER overload response (EOR) and the unfolded protein response (UPR) are activated by mutant C282Y HFE protein.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.