Succinobucol, a Lipid-Lowering Drug, Protects Against 3-Nitropropionic Acid-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Cells via Upregulation of Glutathione Levels and Glutamate Cysteine Ligase Activity

Colle, Dirleise; Santos, Danúbia Bonfanti; Hartwig, Juliana M.; Godoi, Marcelo; Engel, Daiane F.; de, Andreza Fabro; Braga, Antônio L.; Farina, Marcelo

doi:10.1007/s12035-014-9086-x

Cited by 31 publications

(23 citation statements)

References 69 publications

(98 reference statements)

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“…Similarly, Salicylic acid has currently reported to provide neuroprotection against mitochondrial dysfunction, oxidative stress and apoptosis in PD brain due to its antioxidant and anti-inflammatory effects on neuronal cell [110]. Further, potential protective effect of Succinobucol against mitochondrial metabolic impairment and oxidative stress induced by 3-NP has been reported in HD brain [111]. Another biomolecule, N-acetyl-ltryptophan (L-NAT) has been presently reported as an inhibitor of mitochondrial cytochrome c release and thereby acting as a possible neuroprotective agent for ALS [112].…”

Section: Biomolecules Mediated Therapy For Altered Mitochondrial Dynamentioning

confidence: 96%

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Jha

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Mounting evidence suggests a link between metabolic syndrome (MetS) such as diabetes, obesity, non-alcoholic fatty liver disease in the progression of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases (NDDs). For instance, accumulated Aβ oligomer is enhancing neuronal Ca release and neural NO where increased NO level in the brain through post translational modification is modulating the level of insulin production. It has been further confirmed that irrespective of origin; brain insulin resistance triggers a cascade of the neurodegeneration phenomenon which can be aggravated by free reactive oxygen species burden, ER stress, metabolic dysfunction, neuorinflammation, reduced cell survival and altered lipid metabolism. Moreover, several studies confirmed that MetS and diabetic sharing common mechanisms in the progression of AD and NDDs where mitochondrial dynamics playing a critical role. Any mutation in mitochondrial DNA, exposure of environmental toxin, high-calorie intake, homeostasis imbalance, glucolipotoxicity is causative factors for mitochondrial dysfunction. These cumulative pleiotropic burdens in mitochondria leads to insulin resistance, increased ROS production; enhanced stress-related enzymes that is directly linked MetS and diabetes in neurodegeneration. Since, the linkup mechanism between mitochondrial dysfunction and disease phenomenon of both MetS and NDDs is quite intriguing, therefore, it is pertinent for the researchers to identify and implement the therapeutic interventions for targeting MetS and NDDs. Herein, we elucidated the pertinent role of MetS induced mitochondrial dysfunction in neurons and their consequences in NDDs. Further, therapeutic potential of well-known biomolecules and chaperones to target altered mitochondria has been comprehensively documented. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

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Section: Biomolecules Mediated Therapy For Altered Mitochondrial Dynamentioning

confidence: 96%

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Jha

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Nrf2/ARE Signaling Pathways after SCI. Lots of studies have demonstrated that the Nrf2/ARE signaling pathways are essential for the anti-inflammatory and antioxidant properties of metformin [43]. To further determine the mechanism underlying the therapeutic effect of metformin for SCI, we have evaluated whether the Nrf2/ARE signaling pathway is involved in the effect of metformin on SCI.…”

Section: Metformin Reduces Oxidative Stress Via Activating Thementioning

confidence: 99%

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

Wang

Zheng

Han

et al. 2020

Oxidative Medicine and Cellular Longevity

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Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability. Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention. Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders. However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear. In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway. Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo. Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE). Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect. We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro. Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction. Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.

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“…After an appropriate time, the medium was removed and the MTT assay was performed to assess cell viability. For estimation of the potential protective effect of A. asphodeloides, the different combinations of XF and 3-NP were examined (described in detail in Section 4.5) [54].…”

Section: -Np-induced Cytotoxicity In Pc12 Cellsmentioning

confidence: 99%

Anemarrhenae asphodeloides rhizoma Extract Enriched in Mangiferin Protects PC12 Cells against a Neurotoxic Agent-3-Nitropropionic Acid

Piwowar

Rembiałkowska

Rorbach-Dolata

et al. 2020

IJMS

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The rhizome of Anemarrhena asphodeloides Bunge, used in Traditional Chinese Medicine as a brain function-improving herb, is a promising source of neuroprotective substances. The aim of this study was to evaluate the protective action of xanthones from A. asphodeloides rhizomes on the PC12 cell line exposed to the neurotoxic agent—3-nitropropionic acid (3-NP). The xanthone-enriched fraction of the ethanolic extract of A. asphodeloides (abbreviated from now on as XF, for the Xanthone Fraction), rich in polyphenolic xanthone glycosides, in concentrations from 5 to 100 μg/mL, and 3-NP in concentrations from 2.5 to 15 mM, were examined. After 8, 16, 24, 48, and 72 h of exposure of cells to various combinations of 3-NP and XF, the MTT viability assay was performed and morphological changes were estimated by confocal fluorescence microscopy. The obtained results showed a significant increase in the number of cells surviving after treatment with XF with exposure to neurotoxic 3-NP and decreased morphological changes in PC12 cells in a dose and time dependent manner. The most effective protective action was observed when PC12 cells were pre-incubated with the XF. This effect may contribute to the traditional indications of this herb for neurological and cognitive complaints. However, a significant cytotoxicity observed at higher XF concentrations (over 10 µg/mL) and longer incubation time (48 h) requires caution in future research and thorough investigation into potential adverse effects.

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Succinobucol, a Lipid-Lowering Drug, Protects Against 3-Nitropropionic Acid-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Cells via Upregulation of Glutathione Levels and Glutamate Cysteine Ligase Activity

Cited by 31 publications

References 69 publications

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

Anemarrhenae asphodeloides rhizoma Extract Enriched in Mangiferin Protects PC12 Cells against a Neurotoxic Agent-3-Nitropropionic Acid

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