Overexpression of SIRT3 Suppresses Oxidative Stress-induced Neurotoxicity and Mitochondrial Dysfunction in Dopaminergic Neuronal Cells

Lee, Shinrye; Jeon, Yu-Mi; Jo, Myungjin

doi:10.5607/en21021

Cited by 21 publications

(15 citation statements)

References 72 publications

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“…This caused significant memory loss and synaptic dysfunction and was correlated with decreased MMP, increased mitochondrial permeability transition pore opening, and increased mitochondrial apoptosis (Lyu et al 2021). In the same context, SIRT3 overexpression attenuated the neuronal toxicity brought on by astrocytes that were activated by LPS/ interferon-gamma in a coculture of neurons and astrocytes (Lee et al 2021). Besides its role in mitochondrial function, SIRT3 has been documented to induce gene expression of the indispensable fusion protein, MFN2 and increase the activity of OPA1 (Kincaid and Bossy-Wetzel 2013;Meng et al 2019;Ribeiro et al 2019).…”

Section: Discussionmentioning

confidence: 94%

Apigenin attenuates LPS-induced neurotoxicity and cognitive impairment in mice via promoting mitochondrial fusion/mitophagy: role of SIRT3/PINK1/Parkin pathway

et al. 2022

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Rationale Alteration of the NAD+ metabolic pathway is proposed to be implicated in lipopolysaccharide (LPS)-induced neurotoxicity and mitochondrial dysfunction in neurodegenerative diseases. Apigenin, a naturally-occurring flavonoid, has been reported to maintain NAD+ levels and to preserve various metabolic functions. Objectives This study aimed to explore the effect of apigenin on mitochondrial SIRT3 activity as a mediator through which it could modulate mitochondrial quality control and to protect against intracerebrovascular ICV/LPS-induced neurotoxicity. Methods Mice received apigenin (40 mg/kg; p.o) for 7 consecutive days. One hour after the last dose, LPS (12 µg/kg, icv) was administered. Results Apigenin robustly guarded against neuronal degenerative changes and maintained a normal count of intact neurons in mice hippocampi. Consequently, it inhibited the deleterious effect of LPS on cognitive functions. Apigenin was effective in preserving the NAD+/NADH ratio to boost mitochondrial sirtuin-3 (SIRT3), activity, and ATP production. It conserved normal mitochondrial features via induction of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α), along with mitochondrial transcription factor A (TFAM) and the fusion proteins, mitofusin 2 (MFN2), and optic atrophy-1 (OPA1). Furthermore, it increased phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and parkin expression as well as the microtubule-associated protein 1 light chain 3 II/I ratio (LC3II/I) to induce degradation of unhealthy mitochondria via mitophagy. Conclusions These observations reveal the marked neuroprotective potential of apigenin against LPS-induced neurotoxicity through inhibition of NAD+ depletion and activation of SIRT3 to maintain adequate mitochondrial homeostasis and function. Graphical abstract

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Section: Discussionmentioning

confidence: 94%

Apigenin attenuates LPS-induced neurotoxicity and cognitive impairment in mice via promoting mitochondrial fusion/mitophagy: role of SIRT3/PINK1/Parkin pathway

et al. 2022

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“…H 2 O 2 plays a key role in the generation of ROS-associated oxidative stress. H 2 O 2 enters cells rapidly and produces extremely reactive hydroxyl radicals, causing damage to intracellular components such as lipids, proteins, and DNA [ 39 , 40 ]. In contrast, SODs are enzymes that can strongly scavenge superoxide radicals (O 2 − ) and convert them to molecular oxygen and H 2 O 2 [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway

Islam

Shin

Yoo

et al. 2022

BMC Complement Med Ther

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Background Globally, ischemic stroke is a major health threat to humans that causes lifelong disability and death. Mentha arvensis (MA) has been used in traditional medicine to alleviate oxidative stress and inflammation-related disorders. In the present study, the neuroprotective properties of fermented MA (FMA) extract were investigated in the gerbil and SH-SY5Y cells. model of transient global cerebral ischemia. Methods Bilateral common carotid artery occlusion-induced transient global cerebral ischemia in gerbil and hydrogen peroxide (H2O2)-mediated neurotoxic effects in human neuroblastoma cells (SH-SY5Y) were investigated. FMA (400 mg/kg) was orally administered for 7 days before induction of ischemic stroke. To evaluate the neuroprotective activity of FMA, we implemented various assays such as cell viability assay (MTT), lactate dehydrogenase (LDH) assay, histopathology, immunohistochemistry (IHC), histofluorescence, and western blot. Results FMA pretreatment effectively decreased transient ischemia (TI) induced neuronal cell death as well as activation of microglia and astrocytes in the hippocampal region. The protective effects of FMA extract against H2O2-induced cytotoxicity of SH-SY5Y cells were observed by MTT and LDH assay. However, FMA pretreatment significantly increased the expression of the antioxidant marker proteins such as superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) in the hippocampus and SH-SY5Y cells. Furthermore, the activation of mitogen-activated protein kinase (MAPK) further activated a cascade of outcomes such as neuroinflammation and apoptosis. FMA pretreatment notably decreased TI and H2O2 induced activation of MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38) proteins in hippocampus and SH-SY5Y cells respectively. Besides, pretreatment with FMA markedly reduced H2O2 mediated Bax/Bcl2 expression in SH-SY5Y cells. Conclusion Thus, these results demonstrated that neuroprotective activities of FMA might contribute to regulating the MAPK signaling pathway.

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“…Oxidative-stress-induced cytotoxicity by H 2 O 2 is associated with increased production of ROS that damage intracellular molecules including lipids, proteins, and DNA [ 65 , 66 ]. Besides, TI-induced oxidative stress-mediated free radicles increase lipid peroxidation in the CA1 region of the hippocampus [ 40 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Olanzapine Ameliorates Ischemic Stroke-like Pathology in Gerbils and H2O2-Induced Neurotoxicity in SH-SY5Y Cells via Inhibiting the MAPK Signaling Pathway

et al. 2022

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Olanzapine (OLNZ) is used to treat psychotic disorders. To look into the neurological basis of this phenomenon, we investigated the neuroprotective effects of OLNZ in gerbils and SH-SY5Y cells. Gerbils were subjected to transient global cerebral ischemia (TGCI) by blocking both common carotid arteries, and OLNZ (10 mg/kg) was injected intraperitoneally. Hydrogen peroxide (H2O2) was used to induce oxidative-stress-mediated damage in the SH-SY5Y cells. The results indicated that OLNZ administration markedly reduced neuron damage and glial cell triggering within CA1 zone of the hippocampus. We used RNA sequencing to assess the numbers of up-and downregulated genes involved in TGCI. We found that OLNZ treatment downregulated the expression of complement-component-related genes and the expression of mitogen-activated protein kinases (MAPKs) in the hippocampus. In cells, OLNZ co-treatment significantly improved cell viability and reduced lactate dehydrogenase (LDH), and reactive oxygen species (ROS) generation. Expression of antioxidant superoxide dismutase-1,2 enzymes (SOD-1, SOD-2) was also intensely upregulated by OLNZ, while the expression of MAPKs and NF-κB were reduced. Co-incubation with OLNZ also regulated apoptosis-related proteins Bax/Bcl-2 expression. Finally, the results demonstrated that treatment with OLNZ showed neuroprotective effects and that the MAPK pathway could involve in the protective effects.

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Overexpression of SIRT3 Suppresses Oxidative Stress-induced Neurotoxicity and Mitochondrial Dysfunction in Dopaminergic Neuronal Cells

Cited by 21 publications

References 72 publications

Apigenin attenuates LPS-induced neurotoxicity and cognitive impairment in mice via promoting mitochondrial fusion/mitophagy: role of SIRT3/PINK1/Parkin pathway

Apigenin attenuates LPS-induced neurotoxicity and cognitive impairment in mice via promoting mitochondrial fusion/mitophagy: role of SIRT3/PINK1/Parkin pathway

Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway

Olanzapine Ameliorates Ischemic Stroke-like Pathology in Gerbils and H2O2-Induced Neurotoxicity in SH-SY5Y Cells via Inhibiting the MAPK Signaling Pathway

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