Occupatio nal n oise is among the most comm on risks associated with the wellbeing of employees. Occupational exposure to noise causes disabling hearing loss in 16% of adults worldwide.It has bee n ack no wledged that...Occupatio nal n oise is among the most comm on risks associated with the wellbeing of employees. Occupational exposure to noise causes disabling hearing loss in 16% of adults worldwide.It has bee n ack no wledged that no ise-induced heari ng loss (NIHL) is a multifactorial disease, having both genetic and environ mental factors. NIHL continues to be permanent as well as irreversible, but NIHL can be preve nted. As dem on strated by the latest research, excessive oxidative stress in the cochlea has a close link with the pathogenesis of NIHL. which highlights the fact that appropriate control of oxidative stress is a productive strategy for preve nting the in crease in prevale nee and progression of NIHL.展开更多
NFE2-like basic leucine zipper transcription factor 2(NFE2L2,also known as NRF2),is a key transcription factor in the cellular defense against oxidative stress,playing a crucial role in cancer cell survival and resist...NFE2-like basic leucine zipper transcription factor 2(NFE2L2,also known as NRF2),is a key transcription factor in the cellular defense against oxidative stress,playing a crucial role in cancer cell survival and resistance to therapies.This review outlines the current knowledge on the link between NFE2L2 and ferroptosis-a form of regulated cell death characterized by iron-dependent lipid peroxidation-within cancer cells.While NFE2L2 activation can protect normal cells from oxidative damage,its overexpression in cancer cells contributes to drug resistance by upregulating antioxidant defenses and inhibiting ferroptosis.We delve into the molecular pathways of ferroptosis,highlighting the involvement of NFE2L2 and its target genes,such as NQO1,HMOX1,FTH1,FTL,HERC2,SLC40A1,ABCB6,FECH,PIR,MT1G,SLC7A11,GCL,GSS,GSR,GPX4,AIFM2,MGST1,ALDH1A1,ALDH3A1,and G6PD,in ferroptosis resistance.Understanding the delicate balance between NFE2L2’s protective and deleterious roles could pave the way for novel therapeutic strategies targeting NFE2L2 to enhance the efficacy of ferroptosis inducers in cancer therapy.展开更多
Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY ...Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed： a control group （without any treatment）, a genistein group （incubated with 20 μM genistein）, a rote- none group （treated with 50 μM rotenone）, and a rotenone ＋ genistein group （incubated with 20 μM genistein and then treated with 50μM rotenone）. A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin ! levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SYSY cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein ＋ rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers （ICI-182780 and ML385, respectively）, genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson＇s dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.展开更多
基金supported by Outstanding Medical Academic Leaders program of Jiangsu Province [LJ201130]Jiangsu Provincial Youth Medical Talent program [QNRC2016536]+2 种基金Six Talent Peaks Project in Jiangsu Province [WSW-017]Preventive Medicine Foundation of Jiangsu [Y2015049]The Fundamental Research Funds for the Central Universities [3225009404]
文摘Occupatio nal n oise is among the most comm on risks associated with the wellbeing of employees. Occupational exposure to noise causes disabling hearing loss in 16% of adults worldwide.It has bee n ack no wledged that no ise-induced heari ng loss (NIHL) is a multifactorial disease, having both genetic and environ mental factors. NIHL continues to be permanent as well as irreversible, but NIHL can be preve nted. As dem on strated by the latest research, excessive oxidative stress in the cochlea has a close link with the pathogenesis of NIHL. which highlights the fact that appropriate control of oxidative stress is a productive strategy for preve nting the in crease in prevale nee and progression of NIHL.
基金supported by grants from the National Institutes of Health of USA(R01CA160417,R01CA229275,and R01CA211070).
文摘NFE2-like basic leucine zipper transcription factor 2(NFE2L2,also known as NRF2),is a key transcription factor in the cellular defense against oxidative stress,playing a crucial role in cancer cell survival and resistance to therapies.This review outlines the current knowledge on the link between NFE2L2 and ferroptosis-a form of regulated cell death characterized by iron-dependent lipid peroxidation-within cancer cells.While NFE2L2 activation can protect normal cells from oxidative damage,its overexpression in cancer cells contributes to drug resistance by upregulating antioxidant defenses and inhibiting ferroptosis.We delve into the molecular pathways of ferroptosis,highlighting the involvement of NFE2L2 and its target genes,such as NQO1,HMOX1,FTH1,FTL,HERC2,SLC40A1,ABCB6,FECH,PIR,MT1G,SLC7A11,GCL,GSS,GSR,GPX4,AIFM2,MGST1,ALDH1A1,ALDH3A1,and G6PD,in ferroptosis resistance.Understanding the delicate balance between NFE2L2’s protective and deleterious roles could pave the way for novel therapeutic strategies targeting NFE2L2 to enhance the efficacy of ferroptosis inducers in cancer therapy.
基金supported by a grant from the National Key Research and Development Plan of China,No.2016YFC1101500the National Natural Science Foundation of China,No.11672332,11102235,8167050417+1 种基金the Key Science and Technology Support Foundation of Tianjin City of China,No.17YFZCSY00620the Natural Science Foundation of Tianjin City of China,No.15JCYBJC28600,17JCZDJC35400
文摘Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed： a control group （without any treatment）, a genistein group （incubated with 20 μM genistein）, a rote- none group （treated with 50 μM rotenone）, and a rotenone ＋ genistein group （incubated with 20 μM genistein and then treated with 50μM rotenone）. A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin ! levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SYSY cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein ＋ rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers （ICI-182780 and ML385, respectively）, genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson＇s dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.
