为探讨卤代酚复合污染对水生生物的联合毒性效应,探究较为可靠的检测方法,根据所选6种卤代酚化学结构的相似程度和48 h LC50值,将其分为3组二元混合物进行急性暴露实验,毒性单位比为1∶1,每组分2个浓度级别观察金鱼生物学行为的变化,同...为探讨卤代酚复合污染对水生生物的联合毒性效应,探究较为可靠的检测方法,根据所选6种卤代酚化学结构的相似程度和48 h LC50值,将其分为3组二元混合物进行急性暴露实验,毒性单位比为1∶1,每组分2个浓度级别观察金鱼生物学行为的变化,同时检测金鱼肝脏中3种抗氧化酶(SOD,CAT和GSH-Px)活性以及酶活性影响率的变化.结果表明:3组卤代酚对金鱼肝脏中3种抗氧化酶的酶活性影响率变化均有显著性差异(P<0.01);3种抗氧化酶中仅SOD在1/2LC50剂量暴露组中均表现为明显升高的酶活性激活率或酶活性抑制率,提示SOD较适合作为卤代酚低浓度复合水污染情况监测的生物化学检测指标.展开更多
Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o ...Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.展开更多
文摘为探讨卤代酚复合污染对水生生物的联合毒性效应,探究较为可靠的检测方法,根据所选6种卤代酚化学结构的相似程度和48 h LC50值,将其分为3组二元混合物进行急性暴露实验,毒性单位比为1∶1,每组分2个浓度级别观察金鱼生物学行为的变化,同时检测金鱼肝脏中3种抗氧化酶(SOD,CAT和GSH-Px)活性以及酶活性影响率的变化.结果表明:3组卤代酚对金鱼肝脏中3种抗氧化酶的酶活性影响率变化均有显著性差异(P<0.01);3种抗氧化酶中仅SOD在1/2LC50剂量暴露组中均表现为明显升高的酶活性激活率或酶活性抑制率,提示SOD较适合作为卤代酚低浓度复合水污染情况监测的生物化学检测指标.
文摘Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.
