PXD042995

PXD042995 is an original dataset announced via ProteomeXchange.

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

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.

10.1016/j.freeradbiomed.2023.05.018;

10.6019/PXD042995;

submitter keyword: kidney, angiotensin II

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

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PRIDE project URI

• PRIDE
  1. PXD042995
     1. Label: PRIDE project
     2. Name: Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency