scholarly journals Neurotoxic Effect of Ethanolic Extract of Propolis in the Presence of Copper Ions is Mediated through Enhanced Production of ROS and Stimulation of Caspase-3/7 Activity

Toxins ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 273 ◽  
Author(s):  
Vedrana Radovanović ◽  
Josipa Vlainić ◽  
Nikolina Hanžić ◽  
Petra Ukić ◽  
Nada Oršolić ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ethanolic Extract ◽  
Mitogen Activated Protein Kinase ◽  
Enhanced Production ◽  
Toxicological Studies ◽  
Ethanolic Extract Of Propolis

Elevated amounts of copper are considered to be contributing factor in the progression of neurodegenerative diseases as they promote oxidative stress conditions. The aim of our study was to examine the effects of ethanolic extract of propolis (EEP) against copper-induced neuronal damage. In cultured P19 neuronal cells, EEP exacerbated copper-provoked neuronal cell death by increasing the generation of reactive oxygen species (ROS) and through the activation of caspase-3/7 activity. EEP augmented copper-induced up-regulation of p53 and Bax mRNA expressions. Neurotoxic effects of EEP were accompanied by a strong induction of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression and decrease in the expression of c-fos mRNA. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK) prevented detrimental effects of EEP, whereas SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), exacerbated EEP-induced neuronal cell death. Quercetin, a polyphenolic nutraceutical, which is usually present in propolis, was also able to exacerbate copper-induced neuronal death. Our data indicates a pro-oxidative and apoptotic mode of EEP action in the presence of excess copper, wherein ROS/p53/p38 interactions play an important role in death cascades. Our study also pointed out that detailed pharmacological and toxicological studies must be carried out for propolis and other dietary supplements in order to fully recognize the potential adverse effects in specific conditions.

scholarly journals TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

2004 ◽  
Vol 1 (3) ◽  
pp. 263-273 ◽  
Author(s):  
DMITRI LEONOUDAKIS ◽  
STEVEN P. BRAITHWAITE ◽  
MICHAEL S. BEATTIE ◽  
ERIC C. BEATTIE
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Types ◽  
Synaptic Function ◽  
Ampar Trafficking ◽  
Novel Target

Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.

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.

Role of caspase-3 in neuronal cell death

1998 ◽  
Vol 5 ◽  
pp. 207
Author(s):  
A. Gorman ◽  
E. Bonfoco ◽  
B. Zhivotovsky ◽  
S. Orrenius ◽  
S. Ceccatelli
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Oxidative Damage to the Endoplasmic Reticulum is Implicated in Ischemic Neuronal Cell Death

2003 ◽  
Vol 23 (10) ◽  
pp. 1117-1128 ◽  
Author(s):  
Takeshi Hayashi ◽  
Atsushi Saito ◽  
Shuzo Okuno ◽  
Michel Ferrand-Drake ◽  
Robert L Dodd ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Protein Modification ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Transgenic Animals ◽  
Initiation Factor

The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. Because reactive oxygen species (ROS) are robustly produced in the ischemic brain, ER damage by ROS may be implicated in ischemic neuronal cell death. We induced global brain ischemia on wild-type and copper/zinc superoxide dismutase (SOD1) transgenic rats and compared ER stress and neuronal damage. Phosphorylated forms of eukaryotic initiation factor 2α (eIF2α) and RNA-dependent protein kinase-like ER eIF2α kinase (PERK), both of which play active roles in apoptosis, were increased in hippocampal CA1 neurons after ischemia but to a lesser degree in the transgenic animals. This finding, together with the finding that the transgenic animals showed decreased neuronal degeneration, indicates that oxidative ER damage is involved in ischemic neuronal cell death. To elucidate the mechanisms of ER damage by ROS, we analyzed glucose-regulated protein 78 (GRP78) binding with PERK and oxidative ER protein modification. The proteins were oxidatively modified and stagnated in the ER lumen, and GRP78 was detached from PERK by ischemia, all of which were attenuated by SOD1 overexpression. We propose that ROS attack and modify ER proteins and elicit ER stress response, which results in neuronal cell death.

scholarly journals Caspase-3-Like Protease Activity-Independent Apoptosis at the Onset of Neuronal Cell Death in the Gerbil Hippocampus after Global Ischemia

2007 ◽  
Vol 30 (10) ◽  
pp. 1950-1953 ◽  
Author(s):  
Hiroki Shimizu ◽  
Makoto Ohgoh ◽  
Masuhiro Ikeda ◽  
Yukio Nishizawa ◽  
Hiroo Ogura
Keyword(s):  
Cell Death ◽  
Protease Activity ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Global Ischemia

The effect of intracerebroventricular application of the caspase-3 inhibitor zDEVD-FMK on neurological outcome and neuronal cell death after global cerebral ischaemia due to cardiac arrest in rats

Resuscitation ◽  
2008 ◽  
Vol 78 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Peter Teschendorf ◽  
Peter Vogel ◽  
Andreas Wippel ◽  
Jakub J. Krumnikl ◽  
Fabian Spöhr ◽  
...  
Keyword(s):  
Cell Death ◽  
Cardiac Arrest ◽  
Cerebral Ischaemia ◽  
Neurological Outcome ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Global Cerebral Ischaemia

A new technique for real-time analysis of caspase-3 dependent neuronal cell death

2007 ◽  
Vol 161 (2) ◽  
pp. 234-243 ◽  
Author(s):  
Antje Golbs ◽  
Nicolas Heck ◽  
Heiko J. Luhmann
Keyword(s):  
Cell Death ◽  
Real Time ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
New Technique ◽  
Time Analysis ◽  
Real Time Analysis ◽  
A New Technique

scholarly journals Mitogen-activated protein kinase/extracellular signal-regulated kinase attenuates 3-hydroxykynurenine-induced neuronal cell death

2004 ◽  
Vol 88 (3) ◽  
pp. 647-656 ◽  
Author(s):  
Hyun Jung Lee ◽  
Jae-Hyung Bach ◽  
Hee-Sun Chae ◽  
Sang Hyung Lee ◽  
Wan Seok Joo ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

scholarly journals The Efficacy of Cinnamomum burmanii Extract on the Protection of Neuronal Cell Death in Haloperidol Induced Male Wistar Rats

2018 ◽  
Vol 2 (4) ◽  
pp. 1-11
Author(s):  
Nita Parisa ◽  
MT Kamaluddin ◽  
Theodorus Theodorus
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Positive Control ◽  
Control Group ◽  
Cinnamon Extract ◽  
White Rats ◽  
Before And After ◽  
Mean Differences

Background Haloperidol is categorized as the first class antipsychotic drug. Long-term use of haloperidol may convey to increased Reactive Oxygen Species (ROS) that will yield oxidative damage which further leads to cell death. Several studies had identified the effects of cinnamon extract on cell death. This study aimed to determine the efficacy of cinnamon extract (Cinnamomum burmanii) on the protection of neuronal cell death in haloperidol-induced male Wistar white rats. Methods This study was experimental with pre and post-test design. Thirty male Wistar rats were divided into 5 groups, induced with haloperidol and followed by treatment. Caspase-3 and dopamine were assayed by ELISA sandwich method using ELISA kit. Mean difference of caspase expression and dopamine levels before and after induction were shown (p<0.05). Results There were mean differences of caspase-3 expression level in the positive control group, cinnamon extract of 100 and 200mg/kgBW before and after treatment (p<0.05). Whereas for dopamine levels, there were mean differences in positive control group, cinnamon extract of 50, 100 and 200mg/kgBW before and after treatment (p<0.05). With Post Hoc test, it was found that there were no mean differences of caspase-3 expression level between positive group with cinnamon extract group of 100 and 200mg/kgBW (p>0,05) and there were also no mean differences of positive group dopamine level with group of cinnamon extract of 100 and 200mg/kgBW (p>0.05). Conclussion Cinnamomum burmanii extract at dose of 100 and 200mg/kgBW were effective in the protection against neuronal cell death in haloperidol induced male Wistar white rats.

scholarly journals Adrenergic signaling in muscularis macrophages limits neuronal death following enteric infection

2019 ◽  
Author(s):  
Fanny Matheis ◽  
Paul A. Muller ◽  
Christina Graves ◽  
Ilana Gabanyi ◽  
Zachary J. Kerner ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Gastrointestinal Symptoms ◽  
Neuronal Cell ◽  
Neuronal Loss ◽  
Enteric Infection ◽  
Loss Of Function ◽  
Arginase 1 ◽  
Irritable Bowel

SummaryEnteric–associated neurons (EANs) are closely associated with immune cells and continuously monitor and modulate homeostatic intestinal functions, including motility. Bidirectional interactions between immune and neuronal cells are altered during disease processes such as neurodegeneration or irritable bowel syndrome. We investigated how infection-induced inflammation affects intrinsic EANs and the role of intestinalmuscularismacrophages (MMs) in this process. Using murine model of bacterial infection, we observed long-term gastrointestinal symptoms including reduced motility and subtype-specific neuronal loss. Neuronal-specific translational–profiling uncovered a caspase 11–dependent EAN cell–death mechanism induced by enteric infections. MMs responded to luminal infection by upregulating a neuroprotective program; gain– and loss–of-function experiments indicated that β2-adrenergic receptor (β2-AR) signaling in MMs mediates neuronal protection during infection via an arginase 1-polyamine axis. Our results identify a mechanism of neuronal cell death post–infection and point to a role for tissue–resident MMs in limiting neuronal damage.

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