Heme is an important cofactor and a regulatory molecule involved in various physiological processes in virtually all living cellular organisms,and it can also serve as the primary iron source for many bacteria,particu...Heme is an important cofactor and a regulatory molecule involved in various physiological processes in virtually all living cellular organisms,and it can also serve as the primary iron source for many bacteria,particularly pathogens.However,excess heme is cytotoxic to cells.In order to meet physiological needs while preventing deleterious effects,bacteria have evolved sophisti-cated cellular mechanisms to maintain heme homeostasis.Recent advances in technologies have shaped our understanding of the molecular mechanisms that govern the biological processes crucial to heme homeostasis,including synthesis,acquisition,utilization,degradation,trafficking,and efflux,as well as their regulation.Central to these mechanisms is the regulation of the heme,by the heme,and for the heme.In this review,we present state-of-the-art findings covering the biochemical,physio-logical,and structural characterization of important,newly identified hemoproteins/systems involved in heme homeostasis.展开更多
Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mic...Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mice by analyzing the iron binding content,iron circulation,and liver homeostasis.We found that hemoglobin hydrolysate promoted the absorption of non-heme iron with high efficiency in duodenum by spontaneously binding non-heme iron during digestion,and increased hepatic iron content by up-regulating divalent metal transporter 1,zinc transporter 14,but hepatic iron content only increased at 3 weeks.Duodenal iron entered the blood through ferroportin without restriction at 3 weeks,and excessive iron entered the liver and then affected the hepatocyte membranes permeability and lipid synthesis through oxidative stress.With the prolongation of dietary intervention,the up-regulated hepcidin acted on the ferroportin to restrict excess iron from entering the blood,and then the hepatic homeostasis recovered.In addition,hemoglobin hydrolysate enhanced the hepatic antioxidant capacity.Taken together,hemoglobin hydrolysate has a strong ability to promote the absorption of non-heme iron in vivo,and the absorbed iron is relatively safe due to the regulation of hepcidin.展开更多
Inflammation links neurodegenerative,neuropsychiatric and other neurological diseases(NDs)with acute brain events.It is responsible for the alteration of neurotransmission and circuity,brain architecture,and cell fate...Inflammation links neurodegenerative,neuropsychiatric and other neurological diseases(NDs)with acute brain events.It is responsible for the alteration of neurotransmission and circuity,brain architecture,and cell fate,affecting mood and personality(anxiety,depression and schizophrenia)and behavior(decline in cognitive,motor and speech abilities,altered sleep,fatigue,pain sensitivity and dementia).Inflammation is also a key component in systemic chronic diseases(cardiovascular disease,cancer,diabetes,and metabolic syndrome),in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule,and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started.While altered serum bilirubin levels have been reported in ND patients,the potential activity of bilirubin in the brain is vague.This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation,aiming to elucidate the pigment's role in the central nervous system environment.展开更多
Up-regulation of the gene that encodes intracellular heme oxygenase 1 （HO1） benefits plants under cad-mium （Cd2＋） stress; however, the molecular mechanisms remain unclear. Here, we elucidate the role of Arabidops...Up-regulation of the gene that encodes intracellular heme oxygenase 1 （HO1） benefits plants under cad-mium （Cd2＋） stress; however, the molecular mechanisms remain unclear. Here, we elucidate the role of Arabidopsis HY1（AtHO1） in Cd2＋ tolerance by using genetic and molecular approaches. Analysis of two HY1 null mutants, three HY1 over-expression lines, HO double or triple mutants, as well as phyA and phyB mutants revealed the specific hypersensitivityof by1 to Cd2＋ stress. Supplementation with two enzymatic by-products of HY1, carbon monoxide （CO） and iron （Fe,especially）, rescued the Cd2＋-induced inhibition of primary root （PR） elongation in hy1-100. The mutation of HY1, whichexhibited lower glutathione content than Col-0 in root tissues, was able to induce nitric oxide （NO） overproduction,Cd2＋ accumulation, and severe Fe deficiency in root tissues. However, the contrasting responses appeared in 35S：HY1-4.Additionally, reduced levels of Ferric Reduction Oxidase 2 （FRO2） and Iron-Regulated Transporter 1 （IRT1） transcripts,and increased levels of Heavy Metal ATPase 2/4 （HMA2/4） transcripts bolster the notion that HY1 up-regulation amelio-rates Fe deficiency, and might increase Cd2＋ exclusion. Taken together, these results showed that HY1 plays a commonlink in Cd2＋ tolerance by decreasing NO production and improving Fe homeostasis in Arabidopsis root tissues.展开更多
基金This work was supported by the National NaturalScience Foundation of China(Nos.31930003 and 41976087)。
文摘Heme is an important cofactor and a regulatory molecule involved in various physiological processes in virtually all living cellular organisms,and it can also serve as the primary iron source for many bacteria,particularly pathogens.However,excess heme is cytotoxic to cells.In order to meet physiological needs while preventing deleterious effects,bacteria have evolved sophisti-cated cellular mechanisms to maintain heme homeostasis.Recent advances in technologies have shaped our understanding of the molecular mechanisms that govern the biological processes crucial to heme homeostasis,including synthesis,acquisition,utilization,degradation,trafficking,and efflux,as well as their regulation.Central to these mechanisms is the regulation of the heme,by the heme,and for the heme.In this review,we present state-of-the-art findings covering the biochemical,physio-logical,and structural characterization of important,newly identified hemoproteins/systems involved in heme homeostasis.
基金supported by the National Natural Science Foundation of China(32072211)Jiangsu Province Department of Education(Innovation Group of Meat Nutrition and Biotechnology)。
文摘Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mice by analyzing the iron binding content,iron circulation,and liver homeostasis.We found that hemoglobin hydrolysate promoted the absorption of non-heme iron with high efficiency in duodenum by spontaneously binding non-heme iron during digestion,and increased hepatic iron content by up-regulating divalent metal transporter 1,zinc transporter 14,but hepatic iron content only increased at 3 weeks.Duodenal iron entered the blood through ferroportin without restriction at 3 weeks,and excessive iron entered the liver and then affected the hepatocyte membranes permeability and lipid synthesis through oxidative stress.With the prolongation of dietary intervention,the up-regulated hepcidin acted on the ferroportin to restrict excess iron from entering the blood,and then the hepatic homeostasis recovered.In addition,hemoglobin hydrolysate enhanced the hepatic antioxidant capacity.Taken together,hemoglobin hydrolysate has a strong ability to promote the absorption of non-heme iron in vivo,and the absorbed iron is relatively safe due to the regulation of hepcidin.
基金Jayanti S was supported in part by a fellowship from the Lembaga Pengelola Dana Pendidikan of Ministry of Finance of Indonesia and an internal grant from the Italian Liver Foundation.The funders had no role in data analysis and interpretation and also writing of the manuscript
文摘Inflammation links neurodegenerative,neuropsychiatric and other neurological diseases(NDs)with acute brain events.It is responsible for the alteration of neurotransmission and circuity,brain architecture,and cell fate,affecting mood and personality(anxiety,depression and schizophrenia)and behavior(decline in cognitive,motor and speech abilities,altered sleep,fatigue,pain sensitivity and dementia).Inflammation is also a key component in systemic chronic diseases(cardiovascular disease,cancer,diabetes,and metabolic syndrome),in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule,and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started.While altered serum bilirubin levels have been reported in ND patients,the potential activity of bilirubin in the brain is vague.This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation,aiming to elucidate the pigment's role in the central nervous system environment.
文摘Up-regulation of the gene that encodes intracellular heme oxygenase 1 （HO1） benefits plants under cad-mium （Cd2＋） stress; however, the molecular mechanisms remain unclear. Here, we elucidate the role of Arabidopsis HY1（AtHO1） in Cd2＋ tolerance by using genetic and molecular approaches. Analysis of two HY1 null mutants, three HY1 over-expression lines, HO double or triple mutants, as well as phyA and phyB mutants revealed the specific hypersensitivityof by1 to Cd2＋ stress. Supplementation with two enzymatic by-products of HY1, carbon monoxide （CO） and iron （Fe,especially）, rescued the Cd2＋-induced inhibition of primary root （PR） elongation in hy1-100. The mutation of HY1, whichexhibited lower glutathione content than Col-0 in root tissues, was able to induce nitric oxide （NO） overproduction,Cd2＋ accumulation, and severe Fe deficiency in root tissues. However, the contrasting responses appeared in 35S：HY1-4.Additionally, reduced levels of Ferric Reduction Oxidase 2 （FRO2） and Iron-Regulated Transporter 1 （IRT1） transcripts,and increased levels of Heavy Metal ATPase 2/4 （HMA2/4） transcripts bolster the notion that HY1 up-regulation amelio-rates Fe deficiency, and might increase Cd2＋ exclusion. Taken together, these results showed that HY1 plays a commonlink in Cd2＋ tolerance by decreasing NO production and improving Fe homeostasis in Arabidopsis root tissues.
