ArticleFree radical biology & medicine2014
Oxidative stress-mediated aldehyde adduction of GRP78 in a mouse model of alcoholic liver disease: functional independence of ATPase activity and chaperone function.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Molecular regulators of alcoholic liver disease: a comprehensive analysis of microRNAs and long non-coding RNAs.Frontiers in medicine · 2025Review
- Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?Antioxidants (Basel, Switzerland) · 2023Review
- Plasma Proteomic Profile of Patients with Tick-Borne Encephalitis and Co-Infections.International journal of molecular sciences · 2022Article
- Hsp70 in Redox Homeostasis.Cells · 2022Review
- Oxidative Stress-A Key Player in the Course of Alcohol-Related Liver Disease.Journal of clinical medicine · 2021Review
- Co-occurrence of Protein Crotonylation and 2-Hydroxyisobutyrylation in the Proteome of End-Stage Renal Disease.ACS omega · 2021Article
- Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury.Experimental & molecular medicine · 2021Review
- Pharmacological Activation Of Aldehyde Dehydrogenase 2 Protects Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction.Frontiers in immunology · 2021Article
- Harnessing the Proteostasis Network in Alcohol-associated Liver Disease.Current pathobiology reports · 2020Article
- Toxicant-mediated redox control of proteostasis in neurodegeneration.Current opinion in toxicology · 2019Article
- Lipid peroxidation derived reactive aldehydes in alcoholic liver disease.Current opinion in toxicology · 2019Article
- The antioxidant activities of alkalic-extractable polysaccharides from Coprinus comatus on alcohol-induced liver injury in mice.Scientific reports · 2018Article
- Aldehyde-Induced DNA and Protein Adducts as Biomarker Tools for Alcohol Use Disorder.Trends in molecular medicine · 2018Review
- Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH.Free radical biology & medicine · 2017Article
- Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation.Archives of biochemistry and biophysics · 2017Review
- Article
- Oxidative stress and lipotoxicity.Journal of lipid research · 2016Review
- Membrane-associated GRP78 helps subgroup J avian leucosis virus enter cells.Veterinary research · 2016Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pathogenesis in alcoholic liver disease (ALD) is complicated and multifactorial but clearly involves oxidative stress and inflammation. Currently, conflicting reports exist regarding the role of endoplasmic reticulum (ER) stress in the etiology of ALD. The glucose-regulated protein 78 (GRP78) is the ER homolog of HSP70 and plays a critical role in the cellular response to ER stress by serving as a chaperone assisting protein folding and by regulating the signaling of the unfolded protein response (UPR). Comprising three functional domains, an ATPase, a peptide-binding, and a lid domain, GRP78 folds nascent polypeptides via the substrate-binding domain. Earlier work has indicated that the ATPase function of GRP78 is intrinsically linked and essential to its chaperone activity. Previous work in our laboratory has indicated that GRP78 and the UPR are not induced in a mouse model of ALD but that GRP78 is adducted by the lipid electrophiles 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) in vivo. As impairment of GRP78 has the potential to contribute to pathogenesis in ALD, we investigated the functional consequences of aldehyde adduction on GRP78 function. Identification of 4-HNE and 4-ONE target residues in purified human GRP78 revealed a marked propensity for Lys and His adduction within the ATPase domain and a relative paucity of adduct formation within the peptide-binding domain. Consistent with these findings, we observed a concomitant dose-dependent decrease in ATP-binding and ATPase activity without any discernible impairment of chaperone function. Collectively, our data indicate that ATPase activity is not essential for GRP78-mediated chaperone activity and is consistent with the hypothesis that ER stress does not play a primary initiating role in the early stages of ALD.
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