Comparative Proteomic Analysis Shows an Elevation of Mdh1 Associated with Hepatotoxicity Induced by Copper Nanoparticle in Rats

Dong, Shuwei; Gao, Zhaohui; Shen, Xiaoyun; Xue, Huiwen; Li, Xia

doi:10.1016/s2095-3119(13)60389-5

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…The acetylation of MDH1 is one of the cross-talk mechanisms between adipogenesis and intracellular energy levels ( Wang et al, 2010 ). Previous studies have shown that upregulated MDH1 expression can compensate for TCA energy deficiency in rats ( Dong et al, 2014 ). Combined, these data indicate that these acetylated metabolic enzymes are upregulated in the TCA cycle.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice

Wang

Rao

et al. 2021

Front. Mol. Neurosci.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice

Wang

Rao

et al. 2021

Front. Mol. Neurosci.

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“…In this way, expression of those genes can be maintained to compensate for the loss of certain components . Early researches indicate that the expression of MDH1 was regulated so as to compensate the TCA energy deficit in mice . The maintenance of bioenergetic function via compensatory mechanisms including alterations in mitochondrial remodeling or enzyme expression was showed to contribute to preserve function .…”

Section: Discussionmentioning

confidence: 99%

“…44 Early researches indicate that the expression of MDH1 was regulated so as to compensate the TCA energy deficit in mice. 45 The maintenance of bioenergetic function via compensatory mechanisms including alterations in mitochondrial remodeling or enzyme expression was showed to contribute to preserve function. 36 Further exploration required more molecular experiments to validate.…”

Section: ■ Discussionmentioning

confidence: 99%

Oxidative Damage to the TCA Cycle Enzyme MDH1 Dysregulates Bioenergetic Enzymatic Activity in the Aged Murine Brain

et al. 2020

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Aging can have profound effects on the mammalian brain leading to neurodegeneration and cognitive impairment. The brain has exceptionally highenergy requirements and is particularly susceptible to damage within its bioenergetic pathways. Here, we asked how the bioenergetic proteome of the murine brain changed with age and how this might affect brain function. Using label-free LC-MS/ MS proteomics for the discovery phase and quantitative multiple reaction monitoring LC-MRM-MS/MS for the validation phase, we found dysregulated expression of multiple components of the tricarboxylic acid cycle, which is key for mitochondrial energy production, including SULA2, IDH1, IDH2, SDHB, PDHB, MDH1, FH1, and NDUFS3, in old murine brains. We also saw that the oxidoreductases, thioredoxin and glutaredoxin, were significantly down-regulated in the old mouse brain and showed through MS that this correlated with the accumulation of trioxidation in the key metabolic enzyme MDH1 at Cys137. 3D modeling of MDH1 predicted that the damaged sites were located at the protein active zone, and enzymatic kinetic analysis confirmed that MDH1 function was significantly reduced in the old mouse brain. These findings identify the tricarboxylic acid cycle as a key target of degenerative protein modifications with deleterious effects on the aging brain's bioenergetic function.

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“…The available literature indicates that Cu bioavailability can be increased by administering it to rats in the form of Cu nanoparticles (Ognik et al, ). However, due to their specific chemical, physical and catalytic properties, they may exhibit completely different properties than their macro counterparts (Dong, Gao, Shen, Xue, & Li, ). There have been reports that CuNP may have toxic effects on the body, for example, by inducing the production of free radicals such as superoxide anion, hydrogen peroxide and hydroxyl radical.…”

Section: Introductionmentioning

confidence: 99%

The effect of copper nanoparticles and copper (II) salt on redox reactions and epigenetic changes in a rat model

Ognik

Cholewińska

Juśkiewicz

et al. 2019

Animal Physiology Nutrition

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The aim of the study was to evaluate the effects of a diet containing different levels of Cu in two different chemical forms (carbonate and nanoparticles) on redox reactions and epigenetic changes in a rat model. For 4 weeks, five experimental groups (eight rats in each) were fed diets with two dosages of added Cu (standard—6.5 mg/kg or half of the standard dosage—3.25 mg/kg, and as a negative control no additional Cu in the mineral mixture) in two forms (standard—CuCO3 and copper nanoparticles). Addition of Cu nanoparticles resulted in higher Cp (ceruloplasmin) activity and LOOH (lipid peroxides) and MDA (malondialdehyde) content, as well as decrease the CAT (catalase) activity and level of PC (protein carbonyl), 3‐NT (3‐nitrotyrosine), 8‐OHdG (8‐hydroxydeoxyguanosine), GSH + GSSG (total glutathione) and DNA methylation. Reducing the dose of copper resulted in a decrease in the level of LOOH and GSH + GSSG as well as CAT activity, but increased the level of PC and methylated DNA. Based on these evidence, we concluded that addition of copper nanoparticles in the diet reduces protein oxidation and nitration as well as DNA oxidation and methylation. Lowering the level of Cu in the diet increases the oxidation of proteins and DNA methylation.

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Comparative Proteomic Analysis Shows an Elevation of Mdh1 Associated with Hepatotoxicity Induced by Copper Nanoparticle in Rats

Cited by 7 publications

References 27 publications

Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice

Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice

Oxidative Damage to the TCA Cycle Enzyme MDH1 Dysregulates Bioenergetic Enzymatic Activity in the Aged Murine Brain

The effect of copper nanoparticles and copper (II) salt on redox reactions and epigenetic changes in a rat model

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