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PXD042995

PXD042995 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCo-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency
DescriptionKidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of hyper- tension with angiotensin II (Ang II) combined with simvastatin administration results in a high mortality rate or the appearance of signs of kidney failure in heme oxy- genase-1 knockout (HO-1 KO) mice. Here, we aimed to address the mechanisms underlying this effect, focusing on heme and iron metabolism. We show that HO-1 deficiency leads to iron accumulation in the renal cortex. Higher mortality of Ang II and simvastatin-treated HO-1 KO mice coincides with in- creased iron accumulation and the upregulation of mucin-1 in the proximal convoluted tubules. In vitro studies showed that mucin-1 hampers heme- and iron-related oxidative stress through the sialic acid residues. In parallel, knock-down of HO-1 induces the glutathione pathway in an NRF2-depedent manner, which likely protects against heme-induced toxicity. To sum up, we showed that heme degradation during heme overload is not solely dependent on HO-1 enzymatic activity, but can be modulated by the glutathione pathway. We also identified mucin-1 as a novel redox regulator. The results suggest that hypertensive patients with less active HMOX1 alleles may be at higher risk of kidney injury after statin treatment.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:48:44.083.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD042995
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterDominik Cysewski
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-14 15:03:35ID requested
12023-06-19 03:51:04announced
22023-11-14 09:01:00announced2023-11-14: Updated project metadata.
32024-10-22 05:48:44announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.freeradbiomed.2023.05.018;
10.6019/PXD042995;
Kopacz A, Kl, ó, ska D, Cysewski D, Kraszewska I, Przepi, ó, rska K, Lenartowicz M, Ł, oboda A, Grochot-Prz, ę, czek A, Nowak W, J, ó, zkowicz A, Piechota-Pola, ń, czyk A, Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency. Free Radic Biol Med, 205():188-201(2023) [pubmed]
Keyword List
submitter keyword: kidney, angiotensin II
Contact List
Aleksandra Piechota-Polanczyk
contact affiliationDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
contact emailaleksandra.piechota-polanczyk@uj.edu.pl
lab head
Dominik Cysewski
contact affiliationMedical University of Bialystok
contact emaildominikcysewski@gmail.com
dataset submitter
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Dataset FTP location
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