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ARTICLE

Human chemerin induces eryptosis at concentrations exceeding circulating levels

MARYNA TKACHENKO¹, ANATOLII ONISHCHENKO², LILIYA TRYFONYUK³, DMYTRO BUTOV⁴, KATERYNA KOT⁵, VIKTORIIA NOVIKOVA⁶, LIWEI FAN^5,7, VOLODYMYR PROKOPIUK^2,8, YURII KOT^5,*, ANTON TKACHENKO^2,*

1 Department of Internal Medicine No. 2, Clinical Immunology and Allergology, Kharkiv National Medical University, Kharkiv, 61022, Ukraine
2 Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Kharkiv, 61022, Ukraine
3 Institute of Health, National University of Water and Environmental Engineering, Rivne, 61022, Ukraine
4 Department of Infectious Diseases and Phthisiology, Kharkiv National Medical University, Kharkiv, 61022, Ukraine
5 Biochemistry Department, V.N. Karazin Kharkiv National University Ministry of Education and Science of Ukraine, Kharkiv, 61022, Ukraine
6 Department of Chemistry, Biochemistry, Microbiology and Food Hygiene, State Biotechnological University, Kharkiv, 61022, Ukraine
7 Clinical Research Innovation Lab, Floor 26 Block D Qidi Technology Building 8, Tsinghua Technology Park, Beijing, 100084, China
8 Department of Cryobiochemistry, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, 61015, Ukraine

* Corresponding Authors: YURII KOT. Email: ; ANTON TKACHENKO. Email:

(This article belongs to the Special Issue: Cell Death in Health and Disease: Diversity, Complexity, and Dynamics)

BIOCELL 2024, 48(8), 1197-1208. https://doi.org/10.32604/biocell.2024.050206

Received 30 January 2024; Accepted 15 May 2024; Issue published 02 August 2024

Abstract

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood.

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