scholarly journals Pharmacological Inhibition of O-GlcNAc Transferase Promotes mTOR-Dependent Autophagy in Rat Cortical Neurons

2020 ◽  
Vol 10 (12) ◽  
pp. 958
Author(s):  
Md. Ataur Rahman ◽  
Yoonjeong Cho ◽  
Hongik Hwang ◽  
Hyewhon Rhim
Keyword(s):  
Cortical Neurons ◽  
Mtor Inhibitor ◽  
Autophagic Flux ◽  
Autophagosome Formation ◽  
Lysosomotropic Agent ◽  
Rat Cortical Neurons ◽  
Pre Treatment ◽  
Lc3 Puncta ◽  
Glcnac Transferase ◽  
Stimulation Of

O-GlcNAc transferase (OGT) is a ubiquitous enzyme that regulates the addition of β-N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of target proteins. Autophagy is a cellular process of self-digestion, in which cytoplasmic resources, such as aggregate proteins, toxic compounds, damaged organelles, mitochondria, and lipid molecules, are degraded and recycled. Here, we examined how three different OGT inhibitors, alloxan, BXZ2, and OSMI-1, modulate O-GlcNAcylation in rat cortical neurons, and their autophagic effects were determined by immunoblot and immunofluorescence assays. We found that the treatment of cortical neurons with an OGT inhibitor decreased O-GlcNAcylation levels and increased LC3-II expression. Interestingly, the pre-treatment with rapamycin, an mTOR inhibitor, further increased the expression levels of LC3-II induced by OGT inhibition, implicating the involvement of mTOR signaling in O-GlcNAcylation-dependent autophagy. In contrast, OGT inhibitor-mediated autophagy was significantly attenuated by 3-methyladenine (3-MA), a blocker of autophagosome formation. However, when pre-treated with chloroquine (CQ), a lysosomotropic agent and a late-stage autophagy inhibitor, OGT inhibitors significantly increased LC3-II levels along with LC3 puncta formation, indicating the stimulation of autophagic flux. Lastly, we found that OGT inhibitors significantly decreased the levels of the autophagy substrate p62/SQSTM1 while increasing the expression of lysosome-associated membrane protein 1 (LAMP1). Together, our study reveals that the modulation of O-GlcNAcylation by OGT inhibition regulates mTOR-dependent autophagy in rat cortical neurons.

scholarly journals Robust stimulation of TrkB induces delayed increases in BDNF and Arc mRNA expressions in cultured rat cortical neurons via distinct mechanisms

2007 ◽  
Vol 103 (2) ◽  
pp. 626-636 ◽  
Author(s):  
Makoto Yasuda ◽  
Mamoru Fukuchi ◽  
Akiko Tabuchi ◽  
Masahiro Kawahara ◽  
Hiroshi Tsuneki ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Rat Cortical Neurons ◽  
Stimulation Of

Abstract 119: Tempol Pre-treatment Restores Isoflurane Preconditioning in the Aged Cardiomyocytes: Involvement of Pink1/Parkin-mediated Mitophagy

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Li Ma ◽  
Qun Gao ◽  
Mario J Rebecchi ◽  
Lixin Liu
Keyword(s):  
Mitochondrial Protein ◽  
Autophagic Flux ◽  
Fischer 344 ◽  
Protein Ubiquitination ◽  
Chronic Oxidative Stress ◽  
Mitochondrial Functions ◽  
Pre Treatment ◽  
Lc3 Puncta ◽  
Cardiac Preconditioning

Background: Aging is associated with chronic oxidative stress and impaired cardiac preconditioning. Four-week pre-treatment with TEMPOL, an antioxidant, improves mitochondrial functions and restores isoflurane (ISO) preconditioning in the aging rat heart. Because mitophagy is implicated in cardiac preconditioning and declines with age, this study was designed to investigate how age influence mitophagy in response to preconditioning and whether TEMPOL pre-treatment improves it. Methods: Male Fischer 344 old (22-24 months) rats treated with or without 4-week TEMPOL (2 mM in drinking water) and young (4-6 months) untreated rats were used. Cardiomyocytes isolated from these rats were preconditioned with ISO and then collected for Western blot analyses of mitochondrial PINK1, Parkin and ubiquitination, or fixed for IF staining of co-localization of PINK1/Parkin with mitochondria. Autophagic flux was determined by IF staining of LC3 puncta, membrane-associated LC3-II and p62 in the presence and absences of bafilomycin A1, an autophagy inhibitor. ISO preconditioning was assessed by LDH release in a simulated hypoxia/reoxygenation model. Results: ISO protected young but not old cardiomyocytes. Four-week pre-treatment with TEMPOL in vivo restored ISO preconditioning in the old cardiomyocytes. In addition, ISO increased mitochondrial PINK1 and Parkin levels and promoted mitochondrial protein ubiquitination in the young, but not the old cardiomyocytes. TEMPOL pre-treatment improved these responses in the old cardiomyocytes. Aging impaired both baseline and ISO-induced autophagic flux, which was restored by TEMPOL pre-treatment. Inhibition of autophagy by bafilomycin abolished ISO preconditioning in the cardiomyocytes from the young and TEMPOL-pre-treated old rats. Conclusion: Aging reduces PINK1/Parkin-mediated mitophagy in response to ISO and impairs baseline as well as preconditioning-induced autophagic flux. A 4-week pre-treatment of TEMPOL reverses these changes and restores ISO preconditioning in the old cardiomyocytes. Our results may explain why cardiac preconditioning has failed in some clinical trials, because most patients were with pathologies, such as diabetes and advanced age, in which mitophagy is disrupted.

scholarly journals Neuroprotective effects of arbutin against oxygen and glucose deprivation-induced oxidative stress and neuroinflammation in rat cortical neurons

2021 ◽  
Vol 72 (1) ◽  
pp. 123-134
Author(s):  
Jingjing Tan ◽  
Manoj Kumar Yadav ◽  
Sushma Devi ◽  
Manish Kumar
Keyword(s):  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Cultured Neurons ◽  
Neuroprotective Effects ◽  
Oxygen And Glucose Deprivation ◽  
Rat Cortical Neurons ◽  
Pre Treatment ◽  
Factor Α ◽  
The Brain ◽  
Necrosis Factor

Abstract In this study, the neuroprotective potential of arbutin (100 µmol L−1) pre-treatment and post-treatment against oxygen/ glucose deprivation (OGD) and reoxygenation (R) induced ischemic injury in cultured rat cortical neurons was explored. The OGD (60 min) and reoxygenation (24 h) treatment significantly (p < 0.001) compromised the antioxidant defence in cultured neurons. Subsequently, an increase (p < 0.001) in lipid peroxidation and inflammatory cytokines (tumour necrosis factor-α and nuclear factor kappa-B) declined neuron survival. In pre- and post-condition experiments, treatment with arbutin enhanced both survival (p < 0.01) and integrity (p < 0.05) of cultured neurons. Results showed that arbutin protects (p < 0.05) against peroxidative changes, inflammation, and enhanced the antioxidant activity (e.g., glutathione, superoxide dismutase and catalase) in cultured neurons subjected to OGD/R. It can be inferred that arbutin could protect against ischemic injuries and stroke. The anti-ischemic activity of arbutin can arrest post-stroke damage to the brain.

scholarly journals Repeated stimulation of cultured networks of rat cortical neurons induces parallel memory traces

2015 ◽  
Vol 22 (12) ◽  
pp. 594-603 ◽  
Author(s):  
J. le Feber ◽  
T. Witteveen ◽  
T. M. van Veenendaal ◽  
J. Dijkstra
Keyword(s):  
Cortical Neurons ◽  
Repeated Stimulation ◽  
Parallel Memory ◽  
Memory Traces ◽  
Rat Cortical Neurons ◽  
Cultured Networks ◽  
Stimulation Of

The Protective Effects of Jatrorrhizine on β-Amyloid (25-35)-Induced Neurotoxicity in Rat Cortical Neurons

2013 ◽  
Vol 11 (8) ◽  
pp. 1030-1037 ◽  
Author(s):  
Tao Luo ◽  
Wei Jiang ◽  
Yan Kong ◽  
Sheng Li ◽  
Feng He ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Protective Effects ◽  
Rat Cortical Neurons ◽  
Β Amyloid

scholarly journals Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi-An Lin ◽  
Yan-Rong Li ◽  
Yi-Ching Chang ◽  
Mei-Chich Hsu ◽  
Szu-Tah Chen
Keyword(s):  
Mtor Inhibitor ◽  
Signal Pathway ◽  
C2c12 Cells ◽  
Signal Pathways ◽  
Heavy Chains ◽  
Regenerative Effect ◽  
Ampk Phosphorylation ◽  
Pre Treatment ◽  
Myotube Hypertrophy ◽  
C2c12 Myotube

AbstractThe regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.

Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1β Production in Leptomeningeal Cells

2021 ◽  
pp. 1-17
Author(s):  
Wanyi Huang ◽  
Fan Zeng ◽  
Yebo Gu ◽  
Muzhou Jiang ◽  
Xinwen Zhang ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Nlrp3 Inflammasome ◽  
Cortical Neurons ◽  
Inflammasome Activation ◽  
Memory Decline ◽  
Periodontal Bacteria ◽  
Nlrp3 Inflammasome Activation ◽  
Synaptic Failure ◽  
Pre Treatment ◽  
The Impact

Background: Studies have reported that synaptic failure occurs before the Alzheimer’s disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1β in response to systemic inflammation. Objective: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Methods: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1β production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). Results: Systemic P. gingivalis infection increased the expression of IL-1β in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and Cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1β secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. Conclusion: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB/NLRP3 inflammasome-mediated IL-1β production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.

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