Ferroptosis is an iron-driven,phospholipid hydroperoxide-mediated cell death,which has recently emerged as an attractive tool in cancer research due to its ability to govern the anti-tumor immune response.A growing re...Ferroptosis is an iron-driven,phospholipid hydroperoxide-mediated cell death,which has recently emerged as an attractive tool in cancer research due to its ability to govern the anti-tumor immune response.A growing research interest in ferroptosis biology has revealed the contribution of this regulated cell death to multiple diseases.In addition to iron,ferroptosis has been reported to be triggered by multiple heavy metals,which sheds light on the novel aspects of heavy metals-induced cytotoxicity.In this review,the ability of zinc,an essential biogenic element with a wide array of biological functions,to modulate ferroptosis in normal and malignant cells has been summarized.Accumulating evidence suggests that zinc-induced biological effects can be mediated by ferroptosis induction or attenuation.In addition,the anti-cancer effects of zinc can be at least partly attributed to ferroptosis induction.The signaling pathways governing zinc-regulated ferroptosis are highlighted.It has been underscored that zinc-mediated modulation of ferroptosis is dependent on alterations of redox homeostasis,antioxidant defense(in particular,the SLC7A11/GSH/GPX4 axis),and iron metabolism.Additionally,data on ferroptosis induction by zinc oxide nanoparticles are summarized to emphasize the potential of these nanomaterials as a promising therapeutic choice in anti-cancer treatment.展开更多
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,th...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 in blood.展开更多
文摘Ferroptosis is an iron-driven,phospholipid hydroperoxide-mediated cell death,which has recently emerged as an attractive tool in cancer research due to its ability to govern the anti-tumor immune response.A growing research interest in ferroptosis biology has revealed the contribution of this regulated cell death to multiple diseases.In addition to iron,ferroptosis has been reported to be triggered by multiple heavy metals,which sheds light on the novel aspects of heavy metals-induced cytotoxicity.In this review,the ability of zinc,an essential biogenic element with a wide array of biological functions,to modulate ferroptosis in normal and malignant cells has been summarized.Accumulating evidence suggests that zinc-induced biological effects can be mediated by ferroptosis induction or attenuation.In addition,the anti-cancer effects of zinc can be at least partly attributed to ferroptosis induction.The signaling pathways governing zinc-regulated ferroptosis are highlighted.It has been underscored that zinc-mediated modulation of ferroptosis is dependent on alterations of redox homeostasis,antioxidant defense(in particular,the SLC7A11/GSH/GPX4 axis),and iron metabolism.Additionally,data on ferroptosis induction by zinc oxide nanoparticles are summarized to emphasize the potential of these nanomaterials as a promising therapeutic choice in anti-cancer treatment.
文摘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 in blood.
