Human chemerin induces eryptosis at concentrations exceeding circulating levels  

作　　者：MARYNA TKACHENKO ANATOLII ONISHCHENKO LILIYA TRYFONYUK DMYTRO BUTOV KATERYNA KOT VIKTORIIA NOVIKOVA LIWEI FAN VOLODYMYR PROKOPIUK YURII KOT ANTON TKACHENKO 

机构地区：[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

出　　处：《BIOCELL》2024年第8期1197-1208,共12页生物细胞（英文）

摘　　要：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^(21)-Ser^(157) chemerin on eryptosis in vitro.Materials and Methods:Human chemerin 0-2-10-50μg/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^(2+)levels was performed.To supplement data on ROS and Ca^(2+)signaling in chemerin-mediated eryptosis,incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca^(2+)-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^(21)-Ser^(157) chemerin.Results:Our observations suggest that human Glu^(21)-Ser^(157) chemerin had no impact on eryptosis parameters at 2μg/mL.However,chemerin stimulated phosphatidylserine externalization,ROS production,and Ca^(2+)accumulation at higher concentrations suggesting activation of eryptosis.Ca^(2+)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^(21)-Ser^(157) 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^(2+)-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

关 键 词：ADIPOKINE Cell death CHEMERIN Oxidative stress Eryptosis 

分 类 号：Q2[生物学—细胞生物学]