Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

Wang, Xiaofei; Perez, Evelyn; Liu, Ran; Yan, Liang-Jun; Mallet, Robert T.; Yang, Shaohua

doi:10.1016/j.brainres.2006.11.032

Cited by 164 publications

(125 citation statements)

References 56 publications

(34 reference statements)

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“…Enhancing of neuronal defense of pyruvate against 6-OHDA induced cell death has been reported before [12], however, reduced neurotoxic action by pyruvate against 3-HK and salsolinol induced apoptosis we report for the first time. Interestingly, increasing concentrations of pyruvate showed no further improvement of protective effects against 3-HK, 6-OHDA and salsolinol.…”

Section: Discussionsupporting

confidence: 48%

“…Sodium pyruvate, an endogenous low molecular weight antioxidant and energy substrate was found to protect neuronal cells through direct acting in mitochondria by decreasing generation of ROS and stabilization of mitochondrial membrane potential [12]. In various experimental cell models it was also found to protect against such insults as β-amyloid and 6-OHDA [10,13].…”

Section: Introductionmentioning

confidence: 99%

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Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

Wszelaki¹,

Melzig²

2013

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Oxidative stress has been implicated as one of the causes in cell death in many neurodegenerative disorders. Due to antioxidative properties in vitro, the use of flavonoids and other polyphenolic compounds synthesised by plants are considered to be a promising strategy to prevent Alzheimer's disease and Parkinsons's disease. In the present study, we tested protective effects of some polyphenols and sodium pyruvate on 6-hydroxydopamine (6-OHDA), salsolinol and 3-hydroxykynurenine (3-HK) induced neurotoxicity in human neuroblastoma SH-SY5Y cells. We found that luteolin prevented from 6-OHDA and 3-HK induced cell viability reduction and that one of the mechanisms involved in the neuroprotective process was the ability to increase the level of cellular ATP. However, luteolin was ineffective against salsolinol-induced toxicity. Neither pre-treatment with flavonoids nor simultaneous addition had any protective effects on 6-OHDA, salsolinol or 3-HK induced neurotoxicity. Interestingly, both pre-treatment and co-treatment with pyruvate provided protection against 6-OHDA, salsolinol or 3-HK induced toxicity. Moreover, luteolin and sodium pyruvate, administered together, acted additively, so to achieve the same effect, lower concentrations were needed. The ability of luteolin and sodium pyruvate to reduce toxicity of 6-OHDA and 3-HK in SH-SY5Y cells may be related to two different neuroprotective mechanisms and the capability to penetrate into the cell.

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Section: Discussionsupporting

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

Wszelaki¹,

Melzig²

2013

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“…Keto acids have been reported to be chemical scavengers in both bacterial culture and mammalian cells 25,26 . A plausible reaction pathway for the generation of acetate could involve the nucleophilic attack of pyruvate by the reactive oxygen species generated from hydrogen peroxide (H 2 O 2 ) (Fig.…”

Section: Resultsmentioning

confidence: 99%

De novo acetate production is coupled to central carbon metabolism in mammals

Liu

et al. 2018

Preprint

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In cases of nutritional excess, there is incomplete catabolism of a nutritional source and secretion of a waste product (overflow metabolism), such as the conversion of glucose to lactate (the Warburg Effect) in tumors. Here we report that excess glucose metabolism generates acetate, a key nutrient whose source has been unclear. Conversion of pyruvate, the product of glycolysis, to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) a neomorphic enzyme activity from keto acid dehydrogenases that enable it to function as a pyruvate decarboxylase. Furthermore, we demonstrate that glucose-derived acetate is sufficient to maintain acetyl-coenzyme A (Ac-CoA) pools and cell proliferation in certain limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. Thus, de novo acetate production is coupled to the activity of central carbon metabolism providing possible regulatory mechanisms and links to pathophysiology.peer-reviewed)

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“…For flow cytometric analysis, DCFH-DApreloaded cells were incubated in the presence and absence of H 2 O 2 (1 mol ϫ 10 7 cells) for the indicated times at 30°C; DCF fluorescence was measured using a Coulter Epics Elite ESP (Beckman-Coulter) equipped with a 15-milliwatt argon-ion laser (excitation wavelength, 488 nm; emission wavelength, 520 nm) (19). For microplate reader assay, DCFH-DA-preloaded cells were incubated in the presence and absence of H 2 O 2 (0.1 mol ϫ 10 5 cells) for the indicated times at 30°C; DCF fluorescence was measured at 485-nm excitation and 538-nm emission wavelength (20).…”

Section: Yeast Strains Media and Preparation Of Mitochondria Andmentioning

confidence: 99%

Identification and Functional Characterization of a Novel Mitochondrial Carrier for Citrate and Oxoglutarate in Saccharomyces cerevisiae

Castegna

Scarcia

Agrimi

et al. 2010

Journal of Biological Chemistry

112

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Mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides, and coenzymes across the mitochondrial membrane. The function of only a few of the 35 Saccharomyces cerevisiae mitochondrial carriers still remains to be uncovered. In this study, we have functionally defined and characterized the S. cerevisiae mitochondrial carrier Yhm2p. The YHM2 gene was overexpressed in S. cerevisiae, and its product was purified and reconstituted into liposomes. Its transport properties, kinetic parameters, and targeting to mitochondria show that Yhm2p is a mitochondrial transporter for citrate and oxoglutarate. Reconstituted Yhm2p also transported oxaloacetate, succinate, and fumarate to a lesser extent, but virtually not malate and isocitrate. Yhm2p catalyzed only a counter-exchange transport that was saturable and inhibited by sulfhydrylblocking reagents but not by 1,2,3-benzenetricarboxylate (a powerful inhibitor of the citrate/malate carrier). The physiological role of Yhm2p is to increase the NADPH reducing power in the cytosol (required for biosynthetic and antioxidant reactions) and probably to act as a key component of the citrate-oxoglutarate NADPH redox shuttle between mitochondria and cytosol. This protein function is based on observations documenting a decrease in the NADPH/NADP ؉ and GSH/GSSG ratios in the cytosol of ⌬YHM2 cells as well as an increase in the NADPH/ NADP ؉ ratio in their mitochondria compared with wild-type cells. Our proposal is also supported by the growth defect displayed by the ⌬YHM2 strain and more so by the ⌬YHM2⌬ZWF1 strain upon H 2 O 2 exposure, implying that Yhm2p has an antioxidant function.Yhm2p is a protein of unknown function that has been found to be present in the inner mitochondrial membrane of Saccharomyces cerevisiae (1). This protein was shown to complement the growth defect displayed at 37°C by S. cerevisiae cells lacking ABF2, which encodes a mitochondrial DNA-binding protein involved in mitochondrial DNA replication and recombination (1, 2). In addition, the primary structure of Yhm2p exhibits all the characteristic features of the mitochondrial carrier (MC) 3 protein family, i.e. a tripartite structure consisting of three tandemly repeated homologous domains of about 100 amino acids in length, each of which contains a distinct signature motif and two hydrophobic stretches that span the membrane as ␣-helices (for reviews see Refs. 3-5). S. cerevisiae possesses 35 members of this family, one of which is localized in peroxisomes and not in mitochondria. The majority of yeast MCs has been functionally characterized and shown to transport specific metabolites, nucleotides, and coenzymes across the mitochondrial membrane (for review see Ref. 6). By contrast, the substrate(s) transported by Yhm2p have not yet been discovered, and its physiological function is yet unknown.In this study, we provide evidence that the gene product of YMR241w, named Coc1p and known as Yhm2p, is a citrateoxoglutarate carrier in S. cerevisiae. Yhm2p was overexpressed in S....

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Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

Cited by 164 publications

References 56 publications

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

De novo acetate production is coupled to central carbon metabolism in mammals

Identification and Functional Characterization of a Novel Mitochondrial Carrier for Citrate and Oxoglutarate in Saccharomyces cerevisiae

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