PXD042995 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency |
Description | Kidneys 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:48:44.083.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD042995 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Dominik Cysewski |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-06-14 15:03:35 | ID requested | |
1 | 2023-06-19 03:51:04 | announced | |
2 | 2023-11-14 09:01:00 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2024-10-22 05:48:44 | announced | 2024-10-22: 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 affiliation | Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland |
contact email | aleksandra.piechota-polanczyk@uj.edu.pl |
lab head | |
Dominik Cysewski |
contact affiliation | Medical University of Bialystok |
contact email | dominikcysewski@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042995
- Label: PRIDE project
- Name: Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency