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

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 144 ◽  
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.

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

2019 ◽  
Vol 43 (2) ◽  
pp. 326-334 ◽  
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

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

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 867 ◽  
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.

scholarly journals STAT-Dependent Upregulation of 12/15-Lipoxygenase Contributes to Neuronal Injury after Stroke

2015 ◽  
Vol 35 (12) ◽  
pp. 2043-2051 ◽  
Author(s):  
Joo Eun Jung ◽  
Hulya Karatas ◽  
Yu Liu ◽  
Ayfer Yalcin ◽  
Joan Montaner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Injury Mechanism ◽  
Ht22 Cells ◽  
Signal Transducers ◽  
Human Stroke

Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and −1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke.

scholarly journals MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells

2019 ◽  
Vol 20 (10) ◽  
pp. 2504 ◽  
Author(s):  
Mehtab Khan ◽  
Bart P. F. Rutten ◽  
Myeong Ok Kim
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Cell Apoptosis ◽  
High Fat Diet ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Fat ◽  
Ht22 Cells ◽  
Organ Systems

Oxidative stress has been considered as the main mediator in neurodegenerative diseases. A high-fat diet (HFD) and metabolic diseases result in oxidative stress generation, leading to various neurodegenerative diseases via molecular mechanisms that remain largely unknown. Protein kinases play an important role in the homeostasis between cell survival and cell apoptosis. The mammalian sterile 20-like kinase-1 (MST1) protein kinase plays an important role in cellular apoptosis in different organ systems, including the central nervous system. In this study, we evaluated the MST1/c-Jun N-terminal kinase (JNK) dependent oxidative damage mediated cognitive dysfunction in HFD-fed mice and stress-induced hippocampal HT22 (mice hippocampal) cells. Our Western blot and immunofluorescence results indicate that HFD and stress-induced hippocampal HT22 cells activate MST1/JNK/Caspase-3 (Casp-3) signaling, which regulates neuronal cell apoptosis and beta-amyloid-cleaving enzyme (BACE1) expression and leads to impaired cognition. Moreover, MST1 expression inhibition by shRNA significantly reduced JNK/Casp-3 signaling. Our in vivo and in vitro experiments mimicking metabolic stress, such as a high-fat diet, hyperglycemia, and an inflammatory response, determined that MST1 plays a key regulatory role in neuronal cell death and cognition, suggesting that MST1 could be a potential therapeutic target for numerous neurodegenerative diseases.

Acorus calamus extract and its component α-asarone attenuate murine hippocampal neuronal cell death induced by l-glutamate and tunicamycin

2021 ◽  
Vol 85 (3) ◽  
pp. 493-501
Author(s):  
Masashi Mikami ◽  
Ohba Takuya ◽  
Yuta Yoshino ◽  
Shinsuke Nakamura ◽  
Kenichi Ito ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Er Stress ◽  
Biological Activities ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acorus Calamus ◽  
Ros Production ◽  
Ht22 Cells

ABSTRACT The Asian traditional medicinal plant Acorus calamus and its component α-asarone exhibited various biological activities, such as antiinflammation and antioxidant effects. In the present study, we investigated the in vitro effects of A. calamus extract and α-asarone on oxidative stress- and endoplasmic reticulum (ER) stress–induced cell death in hippocampal HT22 cells. A. calamus extract and α-asarone both significantly suppressed cell death induced by the oxidative stress inducer l-glutamate and ER stress inducer tunicamycin. A. calamus extract and α-asarone also significantly reduced reactive oxygen species (ROS) production induced by l-glutamate. Moreover, A. calamus extract and α-asarone suppressed the phosphorylation of protein kinase RNA-like ER kinase (PERK) induced by tunicamycin. These results suggest that A. calamus extract and α-asarone protect hippocampal cells from oxidative stress and ER stress by decreasing ROS production and suppressing PERK signaling, respectively. α-Asarone has potential as a potent therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease.

Histochemical and Fluorescent Analyses of Mitochondrial Integrity in Chick Auditory Neurons following Deafferentation

2010 ◽  
Vol 21 (03) ◽  
pp. 204-218 ◽  
Author(s):  
Hope Elizabeth Karnes ◽  
Peter Nicholas Scaletty ◽  
Dianne Durham
Keyword(s):  
Cell Death ◽  
Mitochondrial Function ◽  
Apoptotic Cell ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Enzyme Reaction ◽  
Oxidative Enzymes ◽  
Mitochondrial Enzymes ◽  
Auditory Neurons ◽  
Mitotracker Red

Background: Neurons rely exclusively on mitochondrial oxidative phosphorylation to meet cellular energy demands, and disruption of mitochondrial function often precipitates neuronal cell death. Auditory neurons in the chick brain stem (n. magnocellularis [NM]) receive glutamatergic innervation exclusively from ipsilateral eighth nerve afferents. Cochlea removal permanently disrupts afferent support and ultimately triggers apoptotic cell death in 30–50% of ipsilateral, deafferented neurons. Here, we evaluated whether disruption of mitochondrial function occurs during deafferentation-induced neuronal cell death. Purpose: To determine whether mitochondrial dysfunction occurs preferentially within dying NM neurons. Research Design: An experimental study. All birds underwent unilateral cochlea removal. Normally innervated neurons contralateral to surgery served as within-animal controls. Study Sample: Hatchling broiler chickens between 8 and 12 days of age served as subjects. A total of 62 birds were included in the study. Intervention: Cochlea removal was performed to deafferent ipsilateral NM neurons and trigger neuronal cell death. Data Collection and Analysis: Following unilateral cochlea removal, birds were sacrificed 12, 24, 48, or 168 hours later, and brain tissue was harvested. Brainstems were sectioned through NM and evaluated histochemically for oxidative enzyme reaction product accumulation or reacted for Mitotracker Red, an indicator of mitochondrial membrane potential (m) and cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL), an indicator of cell death. Histochemical staining intensities for three mitochondrial enzymes, succinate dehydrogenase (SDH), cytochrome c oxidase (CO), and ATP synthase (ATPase) were measured in individual neurons and compared in ipsilateral and contralateral NM. Comparisons were made using unpaired t-tests (CO) or Kruskal Wallis one way ANOVA followed by Dunn's post hoc pairwise comparisons (ATPase, SDH). Mitotracker Red tissue was examined qualitatively for the presence of and extent of colocalization between Mitotracker Red and TUNEL label in NM. Results: Results showed global upregulation of all three oxidative enzymes within deafferented NM neurons compared to contralateral, unperturbed NM neurons. In addition, differential SDH and ATPase staining intensities were detected across neurons within the ipsilateral nucleus, suggesting functional differences in mitochondrial metabolism across deafferented NM. Quantitative analyses revealed that deafferented neurons with preferentially elevated SDH and ATPase activities represent the subpopulation destined to die following cochlea removal. In addition, Mitotracker Red accumulated intensely within the subset of deafferented NM neurons that also exhibited cytoplasmic TdT-mediated dUTP Nick-End Labeling (TUNEL) and subsequently died. Conclusions: Taken together, our results demonstrate that a subset of deafferented NM neurons, presumably those that die, preferentially upregulates SDH, perhaps via the tricarboxylic acid (TCA) cycle. These same neurons undergo ATPase uncoupling and an eventual loss of Δψm.

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