Mn3O4 Nanocrystal-Induced Eryptosis Features Ca2+ Overload, ROS and RNS Accumulation, Calpain Activation, Recruitment of Caspases, and Changes in the Lipid Order of Cell Membranes
Kot Y. Prokopiuk V. Klochkov V. Tryfonyuk L. Maksimchuk P. Aslanov A. Kot K. Avrunin O. Demchenko L. Kurmangaliyeva S. Onishchenko A. Yefimova S. Havranek O. Tkachenko A.
April 2025Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
2025#26Issue 7
Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn3O4 NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn3O4 NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn3O4 NPs was accompanied by Ca2+ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn3O4 NP-induced eryptosis was calpain- and caspase-dependent.
calcium signaling , cytotoxicity , eryptosis , nanoparticles , oxidative stress , regulated cell death
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Department of Biochemistry, V.N. Karazin Kharkiv National, 4 Svobody sq, Kharkiv, 61022, Ukraine
Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, 23 Pereyaslavskaya st, Kharkiv, 61015, Ukraine
Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, 4 Nauky ave, Kharkiv, 61022, Ukraine
Department of Nanostructured Materials, Institute for Scintillation Materials of the National Academy of Sciences of Ukraine, 60 Nauky ave, Kharkiv, 61072, Ukraine
Institute of Health, National University of Water and Environmental Engineering, 11 Soborna st, Rivne, 33028, Ukraine
Department of Biomedical Engineering, Kharkiv National University of Radio Electronics, 14 Nauky ave, Kharkiv, 61116, Ukraine
Department of Chemistry, Stockholm University, Svante Arrhenius väg 16C, Stockholm, SE-106 91, Sweden
Ye.O.Paton Institute of Materials Science and Welding, National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”, 37 Beresteiskyi ave, Kyiv, 03056, Ukraine
Department of Microbiology, Virology and Immunology, West Kazakhstan Marat Ospanov Medical University, 68 Maresyev st, Aktobe, 030012, Kazakhstan
BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, Vestec, 25250, Czech Republic
First Department of Internal Medicine-Hematology, First Faculty of Medicine, Charles University, Prague, 12808, Czech Republic
Universal Scientific Education and Research Network (USERN), Kharkiv, 61022, Ukraine
Department of Biochemistry
Department of Cryobiochemistry
Research Institute of Experimental and Clinical Medicine
Department of Nanostructured Materials
Institute of Health
Department of Biomedical Engineering
Department of Chemistry
Ye.O.Paton Institute of Materials Science and Welding
Department of Microbiology
BIOCEV
First Department of Internal Medicine-Hematology
Universal Scientific Education and Research Network (USERN)
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