Zinc enhances the cellular energy supply to improve cell motility and restore impaired energetic metabolism in a toxic environment induced by OTA

Yang, Xuan; Wang, Haomiao; Huang, Chuchu; He, Xiaoyun; Xu, Wentao; Luo, Yunbo; Huang, Kunlun

doi:10.1038/s41598-017-14868-x

Cited by 33 publications

(19 citation statements)

References 92 publications

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“…(2013) . Studies have shown that the liver lipid metabolism was influenced when rats were given 210 μg/kg body weight OTA ( Qi et al., 2014 ) and decreased the expression of PPARG in human embryonic kidney (HEK) 293 cells treated with OTA ( Yang et al., 2017 ). There was no difference of PPARG expression between CON and OTA groups, which may be due to the animal species and the OTA dosage.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of curcumin on ochratoxin A–induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota

et al. 2020

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Curcumin has antioxidant functions, regulates the intestinal microbial composition, and alleviates mycotoxin toxicity. The present study aimed to explore whether curcumin could alleviate ochratoxin A ( OTA )-induced liver injury via the intestinal microbiota. A total of 720 mixed-sex 1-day-old White Pekin ducklings were randomly assigned into 4 groups: CON (control group, without OTA), OTA (fed a diet with 2 mg/kg OTA), CUR (ducks fed a diet with 400 mg/kg curcumin), and OTA + CUR (2 mg/kg OTA plus 400 mg/kg curcumin). Each treatment consisted of 6 replicates and 30 ducklings per replicate. Treatment lasted for 21 D. Results were analyzed by a two-tailed Student t test between 2 groups. Our results demonstrated that OTA treatment had the highest serum low-density lipoprotein ( LDL ) level among 4 groups. Compared with OTA group, OTA + CUR decreased serum LDL level ( P < 0.05). OTA decreased liver catalase ( CAT ) activity in ducks ( P < 0.05), while addition of curcumin in OTA group increased liver CAT activity ( P < 0.05). 16S ribosomal RNA sequencing suggested that curcumin increased the richness indices (ACE index) and diversity indices (Simpson index) compared with OTA group ( P < 0.05) and recovered the OTA-induced alterations in composition of the intestinal microbiota. Curcumin supplementation relieved the decreased abundance of butyric acid producing bacteria, including blautia , butyricicoccus , and butyricimonas , induced by OTA ( P < 0.05). OTA also significantly influenced the metabolism of the intestinal microbiota, such as tryptophan metabolism and glyceropholipid metabolism. Curcumin could alleviate the upregulation of oxidative stress pathways induced by OTA. OTA treatment also increased SREBP-1c expression ( P < 0.05). The curcumin group had the lowest expression of FAS and PPARG mRNA ( P < 0.05) and the highest expression of NRF2 and HMOX1 mRNA. These results indicated that curcumin could alleviate OTA-induced oxidative injury and lipid metabolism disruption by modulating the cecum microbiota.

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Section: Discussionmentioning

confidence: 99%

Protective effect of curcumin on ochratoxin A–induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota

et al. 2020

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“…In isolated brain mitochondria, submicromolar concentrations of zinc can increase oxygen consumption and reduce reactive oxygen species generation, which led Sensi et al 102 to speculate that mitochondrial zinc pools may have a physiological function for the nervous system. Supplementation of media with added zinc in human embryonic kidney HEK‐293 cells can offset impaired cell viability and motility and improve the cellular energy supply disrupted by ochratoxin A toxicity 103 . Zinc uptake by mitochondria is necessary during neuronal differentiation, and ZIP12 may be part of a pathway that can increase cellular zinc uptake to promote mitochondrial zinc influx.…”

Section: Discussionmentioning

confidence: 99%

“…Supplementation of media with added zinc in human embryonic kidney HEK-293 cells can offset impaired cell viability and motility and improve the cellular energy supply disrupted by ochratoxin A toxicity. 103 Zinc uptake by mitochondria is necessary during neuronal differentiation, and ZIP12 may be part of a pathway that can increase cellular zinc uptake to promote mitochondrial zinc influx. We have previously shown that an increase in Zinpyr-1 fluorescence occurs during Neuro-2a differentiation.…”

Section: Possible Mechanisms For Zinc Influx Through Zinc Transportmentioning

confidence: 99%

Role of zinc transporter ZIP12 in susceptibility‐weighted brain magnetic resonance imaging (MRI) phenotypes and mitochondrial function

et al. 2020

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Brain zinc dysregulation is linked to many neurological disorders. However, the mechanisms regulating brain zinc homeostasis are poorly understood. We performed secondary analyses of brain MRI GWAS and exome sequencing data from adults in the UK Biobank. Coding ZIP12 polymorphisms in zinc transporter ZIP12 (SLC39A12) were associated with altered brain susceptibility weighted MRI (swMRI). Conditional and joint association analyses revealed independent GWAS signals in linkage disequilibrium with 2 missense ZIP12 polymorphisms, rs10764176 and rs72778328, with reduced zinc transport activity. ZIP12 rare coding variants predicted to be deleterious were associated with similar impacts on brain swMRI. In Neuro‐2a cells, ZIP12 deficiency by short hairpin RNA (shRNA) depletion or CRISPR/Cas9 genome editing resulted in impaired mitochondrial function, increased superoxide presence, and detectable protein carbonylation. Inhibition of Complexes I and IV of the electron transport chain reduced neurite outgrowth in ZIP12 deficient cells. Transcriptional coactivator PGC‐1α, mitochondrial superoxide dismutase (SOD2), and chemical antioxidants α‐tocopherol, MitoTEMPO, and MitoQ restored neurite extension impaired by ZIP12 deficiency. Mutant forms of α‐synuclein and tau linked to familial Parkinson’s disease and frontotemporal dementia, respectively, reduced neurite outgrowth in cells deficient in ZIP12. Zinc and ZIP12 may confer resilience against neurological diseases or premature aging of the brain.

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“…Furthermore, in a mouse model of AD, dietary zinc supplementation has been shown to restore impaired mitochondrial respiration and also increase levels of brain-derived neurotrophic factor (BDNF), which itself is linked to mitochondrial dynamics and oxidative efficiency [37,[65][66][67]. The importance of zinc for energy metabolism is further supported by the fact that zinc chelation by N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) results in a 50% reduction of ATP production in hepatocytes [68].…”

Section: Introductionmentioning

confidence: 99%

The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

Liu

Gale

Reynolds³

et al. 2021

Preprint

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Zinc is a highly abundant cation in the brain, where it is essential for cellular function, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc, can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential, leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.

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Zinc enhances the cellular energy supply to improve cell motility and restore impaired energetic metabolism in a toxic environment induced by OTA

Cited by 33 publications

References 92 publications

Protective effect of curcumin on ochratoxin A–induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota

Protective effect of curcumin on ochratoxin A–induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota

Role of zinc transporter ZIP12 in susceptibility‐weighted brain magnetic resonance imaging (MRI) phenotypes and mitochondrial function

The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

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