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PXD035263

PXD035263 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBinding of the spike of SARS-CoV-2 to steatotic hepatocytes promotes metabolic dysfunction
DescriptionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 patients could be attributed to the cytopathic effects induced by the interation between the virus and hepatic cells, exacerbated immune responses or treatment-associated drug toxicity. Here we demonstrate that primary hepatocytes are susceptible to infection in different models: hepatocytes derived from humanized angiotensin-converting enzyme-2 (hACE-2) mice and THLE-2 human cells. Pseudotyped viral particles engineered to express the full-length spike of SARS-CoV-2 and recombinant RBD bind to ACE2 expressed by hepatocytes, promoting metabolic reprogramming towards glycolysis but also mitochondrial dysfunction. In the context of non-alcoholic steatohepatitis (NASH), steatotic hepatocytes derived from hACE2 mice are more vulnerable to infection, as a result of increased expression of ACE2. Metformin, a common therapeutic option for hyperglycemia in type 2 diabetes (T2D) patients, prevents the interaction between the spike of SARS-CoV-2 and steatotic hepatocytes by reducing the expression of hACE2. In summary, we provide evidence that hepatocytes are amenable to SARS-CoV-2 infection and propose metformin as a therapeutic strategy to prevent liver dysfunction caused by SARS-CoV-2 in the context of NASH.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_07:20:34.973.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMikel Azkargorta
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-11 14:48:57ID requested
12022-10-14 03:06:30announced
22023-11-14 07:20:37announced2023-11-14: Updated project metadata.
Publication List
Mercado-G, ó, mez M, Prieto-Fern, á, ndez E, Goikoetxea-Usandizaga N, Vila-Vecilla L, Azkargorta M, Bravo M, Serrano-Maci, á M, Egia-Mendikute L, Rodr, í, guez-Agudo R, Lachiondo-Ortega S, Lee SY, Eguileor Gin, é A, Gil-Pitarch C, Gonz, á, lez-Recio I, Sim, ó, n J, Petrov P, Jover R, Mart, í, nez-Cruz LA, Ere, ñ, o-Orbea J, Delgado TC, Elortza F, Jim, é, nez-Barbero J, Nogueiras R, Prevot V, Palazon A, Mart, í, nez-Chantar ML, The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes. Commun Biol, 5(1):827(2022) [pubmed]
Keyword List
ProteomeXchange project tag: Sars-cov-2, Covid-19
submitter keyword: SARS-CoV-2
hACE2 mice
Liver energy metabolism
NASH
Metformin
Contact List
Felix Elortza
contact affiliationProteomics Service CIC bioGUNE Bizkaia Tech. Park Build. 800 Derio 48160 Spain
contact emailfelortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliationProteomics Platform CIC bioGUNE
contact emailmazkargorta@cicbiogune.es
dataset submitter
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Dataset FTP location
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