CREB and NF-κB Transcription Factors Regulate Sensitivity to Excitotoxic and Oxidative Stress Induced Neuronal Cell Death

Abstract Motoric disturbances in Parkinson’s disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using natural antioxidative flavonoids like Rutin, might provide intervening strategies to improve PD pathogenesis. To explore the potential effects of micro (mRutin) compared to nano Rutin (nRutin) upon the brain and the gut during PD, its neuroprotective effects were assessed using an in vitro PD model. Our results demonstrated that Rutin inhibited the neurotoxicity induced by A53T α-synuclein (Syn) administration by decreasing oxidized lipids and increasing cell viability in both, mesencephalic and enteric cells. For enteric cells, neurite outgrowth, number of synaptic vesicles, and tyrosine hydroxylase positive cells were significantly reduced when treated with Syn. This could be reversed by the addition of Rutin. nRutin revealed a more pronounced result in all experiments. In conclusion, our study shows that Rutin, especially the nanocrystals, are promising natural compounds to protect neurons from cell death and oxidative stress during PD. Early intake of Rutin may provide a realizable option to prevent or slow PD pathogenesis.

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TRPM2 Cation Channels and Oxidative Stress-Induced Neuronal Cell Death

Oxidative Stress in Applied Basic Research and Clinical Practice - Studies on Veterinary Medicine ◽

10.1007/978-1-61779-071-3_4 ◽

2011 ◽

pp. 61-76

Author(s):

Mustafa Naziroğlu

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Cation Channels ◽

And Oxidative Stress

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Lipocalin-2 Deficiency Reduces Oxidative Stress and Neuroinflammation and Results in Attenuation of Kainic Acid-Induced Hippocampal Cell Death

Antioxidants ◽

10.3390/antiox10010100 ◽

2021 ◽

Vol 10 (1) ◽

pp. 100

Author(s):

Hyun Joo Shin ◽

Eun Ae Jeong ◽

Jong Youl Lee ◽

Hyeong Seok An ◽

Hye Min Jang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Kainic Acid ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Lipocalin 2 ◽

Wild Type ◽

Iron Trafficking ◽

Hippocampal Cell ◽

And Oxidative Stress

The hippocampal cell death that follows kainic acid (KA)-induced seizures is associated with blood–brain barrier (BBB) leakage and oxidative stress. Lipocalin-2 (LCN2) is an iron-trafficking protein which contributes to both oxidative stress and inflammation. However, LCN2′s role in KA-induced hippocampal cell death is not clear. Here, we examine the effect of blocking LCN2 genetically on neuroinflammation and oxidative stress in KA-induced neuronal death. LCN2 deficiency reduced neuronal cell death and BBB leakage in the KA-treated hippocampus. In addition to LCN2 upregulation in the KA-treated hippocampus, circulating LCN2 levels were significantly increased in KA-treated wild-type (WT) mice. In LCN2 knockout mice, we found that the expressions of neutrophil markers myeloperoxidase and neutrophil elastase were decreased compared to their expressions in WT mice following KA treatment. Furthermore, LCN2 deficiency also attenuated KA-induced iron overload and oxidative stress in the hippocampus. These findings indicate that LCN2 may play an important role in iron-related oxidative stress and neuroinflammation in KA-induced hippocampal cell death.

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Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Biomolecules & Therapeutics ◽

10.4062/biomolther.2020.154 ◽

2021 ◽

Author(s):

Eun Ji Yeo ◽

Won Sik Eum ◽

Hyeon Ji Yeo ◽

Yeon Joo Choi ◽

Eun Jeong Sohn ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Protective Role ◽

Signal Pathway ◽

Mapk Signal Pathway

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Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽

10.3390/antiox10111702 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1702

Author(s):

Sereen Sandouka ◽

Tawfeeq Shekh-Ahmad

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Status Epilepticus ◽

Temporal Lobe Epilepsy ◽

Antioxidant Capacity ◽

Temporal Lobe ◽

Epileptiform Activity ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

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Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells

Journal of Ginseng Research ◽

10.1016/j.jgr.2018.12.002 ◽

2019 ◽

Vol 43 (2) ◽

pp. 326-334 ◽

Cited By ~ 19

Author(s):

Dong Hoi Kim ◽

Dae Won Kim ◽

Bo Hyun Jung ◽

Jong Hun Lee ◽

Heesu Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Ht22 Cells ◽

Ginsenoside Rb2

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Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽

10.3390/molecules25010144 ◽

2019 ◽

Vol 25 (1) ◽

pp. 144 ◽

Cited By ~ 4

Author(s):

Chang-Hyun Park ◽

Ji Hoon Song ◽

Su-Nam Kim ◽

Ji Hwan Lee ◽

Hae-Jeung Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Protein Kinases ◽

Apoptotic Cell ◽

Curcuma Longa ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Ht22 Cells ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein

In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.

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1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates l-DOPA-Induced Cytotoxicity in PC12 Cells

Molecules ◽

10.3390/molecules24050867 ◽

2019 ◽

Vol 24 (5) ◽

pp. 867 ◽

Cited By ~ 2

Author(s):

Hyun Park ◽

Jong Kang ◽

Myung Lee

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Extracellular Signal ◽

Dopaminergic Neuronal Cell ◽

Mitogen Activated Protein

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ) has previously been found to have effective anti-oxidant and anti-lipid-peroxidative activity. We aimed to elucidate whether HTHQ can prevent dopaminergic neuronal cell death by investigating the effect on l-DOPA-induced cytotoxicity in PC12 cells. HTHQ protected from both l-DOPA-induced cell death and superoxide dismutase activity reduction. When assessing the effect of HTHQ on oxidative stress-related signaling pathways, HTHQ inhibited l-DOPA-induced phosphorylation of sustained extracellular signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1/2). HTHQ also normalized l-DOPA-reduced Bcl-2-associated death protein (Bad) phosphorylation and Bcl-2-associated X protein (Bax) expression, promoting cell survival. Taken together, HTHQ exhibits protective effects against l-DOPA-induced cell death through modulation of the ERK1/2-p38MAPK-JNK1/2-Bad-Bax signaling pathway in PC12 cells. These results suggest that HTHQ may show ameliorative effects against oxidative stress-induced dopaminergic neuronal cell death, although further studies in animal models of Parkinson’s disease are required to confirm this.

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