Inhibition of the Nrf2/HO-1 Axis Suppresses the Mitochondria-Related Protection Promoted by Gastrodin in Human Neuroblastoma Cells Exposed to Paraquat

AbstractMitochondria are double-membrane organelles involved in the transduction of energy from different metabolic substrates into adenosine triphosphate (ATP) in mammalian cells. The oxidative phosphorylation system is comprised by the activity of the respiratory chain and the complex V (ATP synthase/ATPase). This system is dependent on oxygen gas (O2) in order to maintain a flux of electrons in the respiratory chain, since O2 is the final acceptor of these electrons. Electron leakage from this complex system leads to the continuous generation of reactive species in the cells. The mammalian cells exhibit certain mechanisms to attenuate the consequences originated from the constant exposure to these reactive species. In this context, the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and one of the enzymes whose expression is modulated by Nrf2, heme oxygenase-1 (HO-1), take a central role in inducing cytoprotection in humans. Mitochondrial abnormalities are observed during intoxication and in certain diseases, including neurodegeneration. Mitochondrial protection promoted by natural compounds has attracted the attention of researchers due to the promising effects these agents induce experimentally. In this regard, we examined here whether and how gastrodin (GAS), a phenolic glucoside, would prevent the paraquat (PQ)-induced mitochondrial impairment in the SH-SY5Y cells. The cells were exposed to GAS (25  μM) for 4 h prior to the challeng...
Source: Molecular Neurobiology - Category: Neurology Source Type: research

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In this study, we found that Dopamine affects the stability and function of ATG4, a redox-sensitive cysteine-protein involved in the processing of LC3, a key step in the formation of autophagosomes. Resveratrol, a dietary polyphenol with anti-oxidant and pro-autophagic properties, has shown neuroprotective potential in HD. Yet the molecular mechanism through which Resveratrol can protect HD cells against DA is not known. Here, we show that Resveratrol prevents the generation of ROS, restores the level of ATG4, allows the lipidation of LC3, facilitates the degradation of polyQ-Htt aggregates and protects the cells from Dopa...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
In this study, we investigated the neuroprotective effects of GL extract (GLE) and the underlying mechanisms in the classic MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD. Mice were injected with MPTP to induce parkinsonism. Then the mice were administered GLE (400 mg kg-1 d-1, ig) for 4 weeks. We observed that GLE administration significantly improved locomotor performance and increased tyrosine hydroxylase expression in the substantia nigra pars compact (SNpc) of MPTP-treated mice. In in vitro study, treatment of neuroblastoma neuro-2a cells with 1-methyl-4-phenylpyridin...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
Cyanidin is an anthocyanidin extracted from a variety of fruits and vegetables. Cyanidin showed benefits against diabetes, cancer, and atherosclerosis. However, the potential neuroprotective effects of cyanidin against Parkinson ’s disease (PD) have not been examined. Indicated concentrations of cyanidin (1, 3, 10, and 30 μmol/L) were incubated together with 0.5 mmol/L 1-methyl-4-phenylpyridinium (MPP+) to human neuroblastoma SH-SY5Y cells. We found cyanidin prevented MPP+-induced cell demise in a concentration-dependent manner. Cyanidin significantly reduced MPP+-induced apoptosis, this is reflected by decreased ...
Source: Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we found that Dopamine affects the stability and function of ATG4, a redox-sensitive cysteine-protein involved in the processing of LC3, a key step in the formation of autophagosomes. Resveratrol, a dietary polyphenol with anti-oxidant and pro-autophagic properties, has shown neuroprotective potential in HD. Yet the molecular mechanism through which Resveratrol can protect HD cells against DA is not known. Here, we show that Resveratrol prevents the generation of ROS, restores the level of ATG4, allows the lipidation of LC3, facilitates the degradation of polyQ-Htt aggregates and protects the cells from Dopa...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Modification of α-synuclein by lipid peroxidation products derived from polyunsaturated fatty acids promotes toxic oligomerization: its relevance to Parkinson disease. J Clin Biochem Nutr. 2018 May;62(3):207-212 Authors: Shamoto-Nagai M, Hisaka S, Naoi M, Maruyama W Abstract Recently, toxic α-synuclein oligomer, which can mediate cell-to-cell propagation is suggested to cause sporadic Parkinson disease. α-Synuclein interacts with membrane lipids especially polyunsaturated fatty acids to stabilize its three-dementional structure. Peroxidation of polyunsaturated fatty acids may reduce t...
Source: Journal of Clinical Biochemistry and Nutrition - Category: Nutrition Tags: J Clin Biochem Nutr Source Type: research
In this study, we found that Dopamine affects the stability and function of ATG4, a redox-sensitive cysteine-protein involved in the processing of LC3, a key step in the formation of autophagosomes. Resveratrol, a dietary polyphenol with anti-oxidant and pro-autophagic properties, has shown neuroprotective potential in HD. Yet the molecular mechanism through which Resveratrol can protect HD cells against DA is not known. Here, we show that Resveratrol prevents the generation of ROS, restores the level of ATG4, allows the lipidation of LC3, facilitates the degradation of polyQ-Htt aggregates and protects the cells from Dopa...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Cyanidin attenuates Aβ25-35-induced neuroinflammation by suppressing NF-κB activity downstream of TLR4/NOX4 in human neuroblastoma cells. Acta Pharmacol Sin. 2018 Apr 19;: Authors: Thummayot S, Tocharus C, Jumnongprakhon P, Suksamrarn A, Tocharus J Abstract Cyanidin is polyphenolic pigment found in plants. We have previously demonstrated that cyanidin protects nerve cells against Aβ25-35-induced toxicity by decreasing oxidative stress and attenuating apoptosis mediated by both the mitochondrial apoptotic pathway and the ER stress pathway. To further elucidate the molecular mechanisms u...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
Publication date: Available online 29 March 2018 Source:Peptides Author(s): Samyr Machado Querobino, César Augusto João Ribeiro, Carlos Alberto-Silva Bradykinin-potentiating peptides (BPPs – 5a, 7a, 9a, 10c, 11e, and 12b) of Bothrops jararaca (Bj) were described as argininosuccinate synthase (AsS) activators, improving L-arginine availability. Agmatine and polyamines, which are L-arginine metabolism products, have neuroprotective properties. Here, we investigated the neuroprotective effects of low molecular mass fraction from Bj venom (LMMF) and two synthetic BPPs (BPP-10c, <ENWPHPQIPP; BPP-1...
Source: Peptides - Category: Biochemistry Source Type: research
RIP140/PGC-1α axis involved in vitamin A-induced neural differentiation by increasing mitochondrial function. Artif Cells Nanomed Biotechnol. 2018 Mar 07;:1-11 Authors: Mu Q, Yu W, Zheng S, Shi H, Li M, Sun J, Wang D, Hou X, Liu L, Wang X, Zhao Z, Liang R, Zhang X, Dong W, Zeng C, Guo J Abstract Vitamin A deficiency and mitochondrial dysfunction are both associated with neural differentiation-related disorders, such as Alzheimer's disease (AD) and Down syndrome (DS). The mechanism of vitamin A-induced neural differentiation and the notion that vitamin A can regulate the morphology and function of...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
In this study, we report a novel role for TrkAIII in signaling ER stress to the mitochondria in SH-SY5Y NB cells that results in glycolytic metabolic adaptation. The ER stress-inducing agents DTT, A23187 and thapsigargin activated the ER stress-response in control pcDNA SH-SY5Y and TrkAIII expressing SH-SY5Y cells and in TrkAIII SH-SY5Y cells increased TrkAIII targeting to mitochondria and internalisation into inner-mitochondrial membranes. Within inner-mitochondrial membranes, TrkAIII was subjected to Omi/HtrA2-dependent cleavage to tyrosine phosphorylated 45-48kDa carboxyl terminal active fragments, localised predominant...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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