Hofreither, Dominik

Tomin, Tamara

Jahnel, Stefan

Mendjan, Sasha

Schittmayer-Schantl, Matthias

Birner-Grünberger, Ruth

2023-10-24T05:36:50Z

2023-10-24T05:36:50Z

2023-09-27

<div class="csl-bib-body"> <div class="csl-entry">Hofreither, D., Tomin, T., Jahnel, S., Mendjan, S., Schittmayer-Schantl, M., &#38; Birner-Grünberger, R. (2023, September 27). <i>Unraveling Nutrient-Driven Redox Signalling in Failing Hearts: A Mass Spectrometry-Based Investigation of a Novel Cardiac Organoid Model</i> [Poster Presentation]. APMRS 2023, Innsbruck, Austria.</div> </div>

http://hdl.handle.net/20.500.12708/189177

Oxidative stress plays a significant role in the development and progression of various pathologies. In heart failure, a leading cause of death worldwide, oxidative stress is associated with multiple risk factors, such as diabetes and metabolic syndrome. The progression of heart disease is further linked to profound metabolic remodelling, mitochondrial dysfunction and disturbed redox homeostasis. These intercon-nected changes may lead to energy depletion, impaired cardiac function and ultimately heart failure. Based on preliminary data in the tissue of failing hearts, we aimed to design an experimental setup further focusing on cellular changes in vitro. The deployed cardiac models, including human stem cell-derived cardiac organoids (""cardioids"") as well as 2D human cardiomyocyte cell lines (AC16; HCM), were differentially treated to environments reflecting pathological aspects of heart disease. To address the crosstalk of aberrant metabolism and alterations of the myocardial redox state correlated with oxi-dative stress and heart failure, cellular samples were subjected to parallel mass spectrometry-based redox metabolomic and proteomic analyses. Preservative two-step alkylation allowed for the accurate assessment of cellular glutathione redox status as a proxy for oxidative stress and, additionally, the redox status of individual redox-sensitive (cysteine-containing) peptides. Label-free quantitative prote-omics, redox proteomics and untargeted metabolomics were carried out after corresponding chromato-graphic separation on a coupled timsTOF Pro mass spectrometer (Bruker) operated in positive or neg-ative mode, respectively, with enabled trapped ion mobility spectrometry and the scan mode set to par-allel accumulation–serial fragmentation. Targeted redox metabolomics is based on a LCMS-8060 sys-tem (Shimadzu), working in positive multiple reaction monitoring mode for glutathione and its derivatives. Results provide insights into molecular mechanisms of the cellular stress response and metabolism. This includes the adaptive and specific regulation of antioxidative enzymes matching glycolytic and mi-tochondrial flux to preserve redox homeostasis. The experimental setup was further validated by multi-ple signatures matching prior findings in the tissue of failing hearts, including distinct changes in the expression of proteins involved in collagen synthesis and modification, stress-mediated extracellular matrix remodelling, lipid metabolism and ion transport. Further efforts to mature and thereby improve the translational ability of the cardiac in vitro models to drive our investigation of nutrient-driven redox signalling have been productive. Follow-up experiments on potential key mediators between metabolism and oxidative stress, as identi-fied by redox proteomics, are being carried out. In conclusion, elucidation of the intricate pathophysio-logical events in heart failure requires profound analytical methods and the utilization of cardiac in vitro models appropriate to their respective translational ability to drive the discovery and validation of novel strategies in diagnosis and treatment.

FWF Fonds zur Förderung der wissenschaftlichen Forschung (FWF)

en

heart failure

oxidative stress

proteomics

Unraveling Nutrient-Driven Redox Signalling in Failing Hearts: A Mass Spectrometry-Based Investigation of a Novel Cardiac Organoid Model

Presentation

Vortrag

Austrian Academy of Sciences, Austria

Austrian Academy of Sciences, Austria

F 7309-B21

Poster Presentation

Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten

M6

Biological and Bioactive Materials

100

https://biocrates.com/event/apmrs-2023/

E164-01-3 - Forschungsgruppe Bioanalytik

0000-0002-7071-2316

0000-0003-1147-9179

0000-0001-7539-3951

0000-0003-3249-655X

0000-0003-3950-0312

APMRS 2023

27-09-2023

29-09-2023

On Site

Event for scientific audience

Innsbruck

AT

Hofreither, Dominik

Chemie

Biologie

Anatomie, Pathologie, Physiologie

1040

1060

3011

40

30

30

http://purl.org/coar/resource_type/c_18co

conference poster not in proceedings

Publications

no Fulltext

en

restricted

FWF - Österr. Wissenschaftsfonds

F 7309-B21

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01-3 - Forschungsgruppe Bioanalytik

Austrian Academy of Sciences

Austrian Academy of Sciences

E164-01-3 - Forschungsgruppe Bioanalytik

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

0000-0002-7071-2316

0000-0003-1147-9179

0000-0001-7539-3951

0000-0003-3249-655X

0000-0003-3950-0312

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

E164 - Institut für Chemische Technologien und Analytik