scholarly journals Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1231 ◽  
Author(s):  
Kinga Rusinek ◽  
Przemysław Sołek ◽  
Anna Tabęcka-Łonczyńska ◽  
Marek Koziorowski ◽  
Jennifer Mytych
Keyword(s):  
Er Stress ◽  
Neurodegenerative Disorders ◽  
Hippocampal Neurons ◽  
Nitrosative Stress ◽  
Defense Mechanism ◽  
Mapk Pathway ◽  
Apoptotic Cell ◽  
Neuronal Cells ◽  
Lps Challenge

Neuroinflammation is defined as the activation of the brain’s innate immune system in response to an inflammatory challenge and is considered to be a prominent feature of neurodegenerative diseases. The contribution of overactivated neuroglial cells to neuroinflammation and neurodegenerative disorders is well documented, however, the role of hippocampal neurons in the neuroinflammatory process remains fragmentary. In this study, we show for the first time, that klotho acts as a signal transducer between pro-survival and pro-apoptotic crosstalk mediated by ER stress in HT-22 hippocampal neuronal cells during LPS challenge. In control HT-22 cells, LPS treatment results in activation of the IRE1α-p38 MAPK pathway leading to increased secretion of anti-inflammatory IL-10, and thus, providing adaptation mechanism. On the other hand, in klotho-deficient HT-22 cells, LPS induces oxi-nitrosative stress and genomic instability associated with telomere dysfunctions leading to p53/p21-mediated cell cycle arrest and, in consequence, to ER stress, inflammation as well as of apoptotic cell death. Therefore, these results indicate that klotho serves as a part of the cellular defense mechanism engaged in the protection of neuronal cells against LPS-mediated neuroinflammation, emerging issues linked with neurodegenerative disorders.

scholarly journals Key Role of Cytochrome C for Apoptosis Detection Using Raman Microimaging in an Animal Model of Brain Ischemia with Insulin Treatment

2019 ◽  
Vol 73 (10) ◽  
pp. 1208-1217 ◽  
Author(s):  
Vanessa Russo ◽  
Patrizio Candeloro ◽  
Natalia Malara ◽  
Gerardo Perozziello ◽  
Michelangelo Iannone ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Brain Ischemia ◽  
Hippocampal Neurons ◽  
Apoptotic Cell ◽  
Resonant Scattering ◽  
Global Ischemia ◽  
Alternative Mechanism ◽  
Mongolian Gerbils ◽  
Incident Wavelength

Brain ischemia represents a leading cause of death and disability in industrialized countries. To date, therapeutic intervention is largely unsatisfactory and novel strategies are required for getting better protection of neurons injured by cerebral blood flow restriction. Recent evidence suggests that brain insulin leads to protection of neuronal population undergoing apoptotic cell death via modulation of oxidative stress and mitochondrial cytochrome c (CytC), an effect to be better clarified. In this work, we investigate on the effect of insulin given intracerebroventricular (ICV) before inducing a transient global ischemia by bilateral occlusion of the common carotid arteries (BCCO) in Mongolian gerbils (MG). The transient (3 min) global ischemia in MG is observed to produce neurodegenerative effect mainly into CA3 hippocampal region, 72 h after cerebral blood restriction. Intracerebroventricular microinfusion of insulin significantly prevents the apoptosis of CA3 hippocampal neurons. Histological observation, after hematoxylin and eosin staining, puts in evidence the neuroprotective role of insulin, but Raman microimaging provides a clearer insight in the CytC mechanism underlying the apoptotic process. Above all, CytC has been revealed to be an outstanding, innate Raman marker for monitoring the cells status, thanks to its resonant scattering at 530 nm of incident wavelength and to its crucial role in the early stages of cells apoptosis. These data support the hypothesis of an insulin-dependent neuroprotection and antiapoptotic mechanism occurring in the brain of MG undergoing transient brain ischemia. The observed effects occurred without any peripheral change on serum glucose levels, suggesting an alternative mechanism of insulin-induced neuroprotection.

scholarly journals JNK1/2 regulates ER–mitochondrial Ca2+ cross-talk during IL-1β–mediated cell death in RINm5F and human primary β-cells

2013 ◽  
Vol 24 (12) ◽  
pp. 2058-2071 ◽  
Author(s):  
Gaurav Verma ◽  
Himanshi Bhatia ◽  
Malabika Datta
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Mitochondrial Permeability Transition ◽  
Apoptotic Cell ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Β Cells ◽  
Mediating Role ◽  
Induced Apoptosis

Elevated interleukin-1β (IL-1β) induces apoptosis in pancreatic β-cells through endoplasmic reticulum (ER) stress induction and subsequent c-jun-N-terminal kinase 1/2 (JNK1/2) activation. In earlier work we showed that JNK1/2 activation is initiated before ER stress and apoptotic induction in response to IL-1β. However, the detailed regulatory mechanisms are not completely understood. Because the ER is the organelle responsible for Ca2+ handling and storage, here we examine the effects of IL-1β on cellular Ca2+ movement and mitochondrial dysfunction and evaluate the role of JNK1/2. Our results show that in RINm5F cells and human primary β-cells, IL-1β alters mitochondrial membrane potential, mitochondrial permeability transition pore opening, ATP content, and reactive oxygen species production and these alterations are preceded by ER Ca2+ release via IP3R channels and mitochondrial Ca2+ uptake. All these events are prevented by JNK1/2 small interfering RNA (siRNA), indicating the mediating role of JNK1/2 in IL-1β–induced cellular alteration. This is accompanied by IL-1β–induced apoptosis, which is prevented by JNK1/2 siRNA and the IP3R inhibitor xestospongin C. This suggests a regulatory role of JNK1/2 in modulating the ER-mitochondrial-Ca2+ axis by IL-1β in apoptotic cell death.

Proteomic profile of 4-PBA treated human neuronal cells during ER stress

2018 ◽  
Vol 14 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Bhavneet Kaur ◽  
Ajay Bhat ◽  
Rahul Chakraborty ◽  
Khushboo Adlakha ◽  
Shantanu Sengupta ◽  
...  
Keyword(s):  
Er Stress ◽  
Neuronal Cells ◽  
Proteomic Profile ◽  
Chemical Chaperone ◽  
Human Neuronal Cells

Global proteomics supports the role of 4-PBA as a chemical chaperone in alleviating neurotoxicity during ER stress.

scholarly journals Antioxidant Role of Kaempferol in Prevention of Hepatocellular Carcinoma

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1419
Author(s):  
Nidhi Sharma ◽  
Subhrajit Biswas ◽  
Noura Al-Dayan ◽  
Alaa Saud Alhegaili ◽  
Maryam Sarwat
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Er Stress ◽  
Defense Mechanism ◽  
Aloe Vera ◽  
Crocus Sativus ◽  
Potential Candidate ◽  
Dietary Flavonoid ◽  
Cellular Stresses

Reactive oxygen species (ROS) are noxious to cells because their increased level interacts with the body’s defense mechanism. These species also cause mutations and uncontrolled cell division, resulting in oxidative stress (OS). Prolonged oxidative stress is responsible for incorrect protein folding in the endoplasmic reticulum (ER), causing a stressful condition, ER stress. These cellular stresses (oxidative stress and ER stress) are well-recognized biological factors that play a prominent role in the progression of hepatocellular carcinoma (HCC). HCC is a critical global health problem and the third leading cause of cancer-related mortality. The application of anti-oxidants from herbal sources significantly reduces oxidative stress. Kaempferol (KP) is a naturally occurring, aglycone dietary flavonoid that is present in various plants (Crocus sativus, Coccinia grandis, Euphorbia pekinensis, varieties of Aloe vera, etc.) It is capable of interacting with pleiotropic proteins of the human body. Efforts are in progress to develop KP as a potential candidate to prevent HCC with no adverse effects. This review emphasizes the molecular mechanism of KP for treating HCC, targeting oxidative stress.

scholarly journals Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Karan Naresh Amin ◽  
Palanisamy Rajagru ◽  
Koustav Sarkar ◽  
M. R. Ganesh ◽  
Takayoshi Suzuki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Target Genes ◽  
Defense Mechanism ◽  
Redox Homeostasis ◽  
Related Factor ◽  
Protective Mechanisms ◽  
Nrf2 Activator

Endoplasmic reticulum (ER) plays a key role in the folding, modification, and trafficking of proteins. When the homeostasis of the ER is disturbed, un/misfolded proteins accumulate in the ER which leads to ER stress. Sustained ER stress results in apoptosis, which is associated with various diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor in redox homeostasis by regulating various genes associated with detoxification and cell-protective mechanisms. We found that Rosolic acid (RA) treatment dose-dependently activates Nrf2 in endothelial cells using the enzyme fragment complementation assay. The cytoprotective role of RA against ER stress-induced endothelial apoptosis and its molecular mechanism was explored in the present study. The Nrf2 and its target genes, as well as ER stress marker expressions, were measured by qPCR in ER stress-exposed endothelial cells. The contribution of Nrf2 in RA-mediated defense mechanism in endothelial cells was established by knockout studies using Nrf2-CRISPR/Cas9. The treatment with RA to ER stress-induced endothelial cells exhibited activation of Nrf2, as demonstrated by Nrf2 translocation and reduction of ER stress markers. We found that the Nrf2 knockout sensitized the endothelial cells against ER stress, and further, RA failed to mediate its cytoprotective effect. Proteomic studies using LC-MS/MS revealed that among the 1370 proteins detected, we found 296 differentially regulated proteins in ER stress-induced endothelial cells, and RA administration ameliorated 71 proteins towards the control levels. Of note, the ER stress in endothelial cells was attenuated by the treatment with the RA, suggesting the role of the Nrf2 activator in the pathological conditions of ER stress-associated diseases.

scholarly journals 3 β-Hydroxysteroid-Δ 24 Reductase (DHCR24) Protects Neuronal Cells from Apoptotic Cell Death Induced by Endoplasmic Reticulum (ER) Stress

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86753 ◽  
Author(s):  
Xiuli Lu ◽  
Yang Li ◽  
Weiqi Wang ◽  
Shuchao Chen ◽  
Ting Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Neuronal Cells ◽  
Apoptotic Cell Death

scholarly journals Regulation of morphine-induced synaptic alterations: Role of oxidative stress, ER stress, and autophagy

2016 ◽  
Vol 215 (2) ◽  
pp. 245-258 ◽  
Author(s):  
Yu Cai ◽  
Lu Yang ◽  
Guoku Hu ◽  
Xufeng Chen ◽  
Fang Niu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Er Stress ◽  
Hippocampal Neurons ◽  
Therapeutic Interventions ◽  
Platelet Derived Growth Factor ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Μ Opioid Receptor ◽  
Sequential Induction

Our findings suggest that morphine dysregulates synaptic balance in the hippocampus, a key center for learning and memory, via a novel signaling pathway involving reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy. We demonstrate in this study that exposure of morphine to hippocampal neurons leads to a reduction in excitatory synapse densities with a concomitant enhancement of inhibitory synapse densities via activation of the μ opioid receptor. Furthermore, these effects of morphine are mediated by up-regulation of intracellular ROS from NADPH oxidase, leading, in turn, to sequential induction of ER stress and autophagy. The detrimental effects of morphine on synaptic densities were shown to be reversed by platelet-derived growth factor (PDGF), a pleiotropic growth factor that has been implicated in neuroprotection. These results identify a novel cellular mechanism involved in morphine-mediated synaptic alterations with implications for therapeutic interventions by PDGF.

scholarly journals The Role of Human Coactosin-Like Protein in Neurodegenerative Disorders

2017 ◽  
pp. 20-24
Author(s):  
Y Anu Shanu ◽  
Antonio Lauto ◽  
Simon J Myers
Keyword(s):  
Actin Cytoskeleton ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Binding Proteins ◽  
Neuronal Cells ◽  
Actin Binding ◽  
Actin Binding Proteins

Coactosin is one of the numerous actin-binding proteins which regulate the actin cytoskeleton. Coactosin binds F-actin, and also interacts with 5-lipoxygenase, which is the first committed enzyme in leukotriene biosynthesis. Coactosin and human coactosin like protein 1 (COTL1) have the potential to play a role in the degradation or impairment of neuronal cells and their functioning. Its homology to other proteins that affect neuronal cells also contributes to this notion. The objective of this review is to explore its structural novelty, regulation and its significance in neurodegenerative diseases.

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