Dysregulation of miRNA and its reversal with l-ascorbic acid during AGE-BSA induced ER stress in Mus musculus neuronal cells

Methamphetamine (METH) is a highly addictive drug that induces irreversible damage to neuronal cells and pathological malfunction in the brain. Aromadendrin, isolated from the flowers of Chionanthus retusus, has been shown to have anti-inflammatory or anti-tumor activity. Nevertheless, it has been reported that METH exacerbates neurotoxicity by inducing endoplasmic reticulum (ER) stress via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in neuronal cells. There is little evidence that aromadendrin protects cells from neurotoxicity induced by METH. In this study, we found that aromadendrin partially suppressed the METH-induced cell death in SH-SY5y cells without causing cytotoxicity. Aromadendrin regulated METH-induced ER stress by preserving the phosphorylation of the PI3K/Akt/mTOR signaling pathway in METH-exposed SH-SY5y cells. In addition, aromadendrin mitigated METH-induced autophagic and the apoptotic pathways in METH-exposed SH-SY5y cells. Mechanistic studies revealed that pre-treatment with aromadendrin restored the expression of anti-apoptotic proteins in METH-exposed conditions. The inhibitor assay confirmed that aromadendrin-mediated restoration of mTOR phosphorylation protected cells from autophagy and apoptosis in METH-exposed cells. Therefore, these findings suggest that aromadendrin relatively has a protective effect on SH-SY5y cells against autophagy and apoptosis induced by METH via regulation of ER stress and the PI3K/Akt/mTOR signaling pathway.

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Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells

Archives of Toxicology ◽

10.1007/s00204-016-1835-3 ◽

2016 ◽

Vol 91 (4) ◽

pp. 1847-1858 ◽

Cited By ~ 15

Author(s):

Mohammed Qaisiya ◽

Cristina Brischetto ◽

Jana Jašprová ◽

Libor Vitek ◽

Claudio Tiribelli ◽

...

Keyword(s):

Inflammatory Response ◽

Er Stress ◽

Neuronal Cells

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The Molecular Mechanism of Endoplasmic Reticulum Stress-Induced Apoptosis in PC-12 Neuronal Cells: The Protective Effect of Insulin-Like Growth Factor I

Endocrinology ◽

10.1210/en.2008-0794 ◽

2008 ◽

Vol 150 (1) ◽

pp. 277-285 ◽

Cited By ~ 55

Author(s):

Cheng-Gang Zou ◽

Xiu-Zhen Cao ◽

Yue-Shui Zhao ◽

Shun-Yu Gao ◽

Shu-De Li ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Protective Effect ◽

Er Stress ◽

P38 Mapk ◽

Neuronal Apoptosis ◽

Neuronal Cells ◽

Dependent Manner ◽

Related Protein ◽

Igf I ◽

Induced Apoptosis

Endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative diseases. Although CCAAT/enhancer-binding protein homologous protein (CHOP) has been shown to play a critical role in ER stress, the precise apoptosis cascade downstream of CHOP is unknown. In this report, we investigated the mechanism of ER stress-mediated apoptosis as well as the action of IGF-I in PC-12 neuronal cells. Our results demonstrated that tribbles-related protein 3 (TRB3), which is a target gene of CHOP, was responsible for tunicamycin (an ER stress inducer)-induced apoptosis. TRB3 could promote dephosphorylation of Akt in PC-12 cells. IGF-I inhibited ER stress-induced apoptosis by restoring the phosphorylation level of Akt. Both wortmannin (a phosphatidylinositide 3-kinase inhibitor) and SB 212090 (a p38 MAPK inhibitor) suppressed the protective effect of IGF-I on ER stress-induced apoptosis. Interestingly, IGF-I attenuated ER stress-mediated expression of TRB3 but not CHOP. This action of IGF-I was abolished by SB 212090 but not by wortmannin. Immunoprecipitation analysis revealed that IGF-I promoted the phosphorylation of CHOP by activating p38 MAPK, probably leading to a decrease in the transcriptional activity of CHOP. The dephosphorylation of Akt resulted in increased expression of a proapoptotic protein, p53 up-regulated modulator of apoptosis (PUMA), in a forkhead box O3a-dependent manner. Knockdown of PUMA by short hairpin RNA attenuated ER stress-mediated apoptosis. Thus, our current study indicates that both TRB3 and PUMA are critical molecules in ER stress-induced apoptosis. IGF-I effectively protects PC-12 neuronal cells against ER stress-induced apoptosis through the phosphatidylinositide 3-kinase/Akt and p38 MAPK pathways. Endoplasmic reticulum (ER) stress causes neuronal apoptosis by inducing the expression of tribbles-related protein 3 and PUMA. IGF-1 prevents neuronal apoptosis against ER stress through phosphatidylinositide 3-kinase/Akt and p38 mitogen-activated protein kinase pathways.

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

Molecular Omics ◽

10.1039/c7mo00114b ◽

2018 ◽

Vol 14 (1) ◽

pp. 53-63 ◽

Cited By ~ 10

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.

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

Cells ◽

10.3390/cells9051231 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1231 ◽

Cited By ~ 1

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.

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Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells

British Journal Of Nutrition ◽

10.1017/s000711451300086x ◽

2013 ◽

Vol 110 (9) ◽

pp. 1549-1558 ◽

Cited By ~ 9

Author(s):

Takuya Sakurai ◽

Kentaro Kitadate ◽

Hiroshi Nishioka ◽

Hajime Fujii ◽

Junetsu Ogasawara ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Cognitive Impairment ◽

Er Stress ◽

Conditioned Fear ◽

Neuronal Cells ◽

Specific Inhibitor ◽

Fear Memory ◽

Pcr Analysis ◽

Samp8 Mice ◽

Senescence Accelerated Mice

Recently, the ability of polyphenols to reduce the risk of dementia and Alzheimer's disease (AD) has attracted a great deal of interest. In the present study, we investigated the attenuating effects of oligomerised lychee fruit-derived polyphenol (OLFP, also called Oligonol) on early cognitive impairment. Male senescence-accelerated mouse prone 8 (SAMP8) mice (4 months old) were given OLFP (100 mg/kg per d) for 2 months, and then conditioned fear memory testing was conducted. Contextual fear memory, which is considered hippocampus-dependent memory, was significantly impaired in SAMP8 mice compared with non-senescence-accelerated mice. OLFP attenuated cognitive impairment in SAMP8 mice. Moreover, the results of real-time PCR analysis that followed DNA array analysis in the hippocampus revealed that, compared with SAMP8 mice, the mRNA expression of Wolfram syndrome 1 (Wfs1) was significantly higher in SAMP8 mice administered with OLFP. Wfs1 reportedly helps to protect against endoplasmic reticulum (ER) stress, which is thought to be one of the causes for AD. The expression of Wfs1 was significantly up-regulated in NG108-15 neuronal cells by the treatment with OLFP, and the up-regulation was inhibited by the treatment of the cells with a c-Jun N-terminal kinase-specific inhibitor rather than with an extracellular signal-regulated kinase inhibitor. Moreover, OLFP significantly attenuated the tunicamycin-induced expression of the ER stress marker BiP (immunoglobulin heavy chain-binding protein) in the cells. These results suggest that OLFP has an attenuating effect on early cognitive impairment in SAMP8 mice, and diminishes ER stress in neuronal cells.

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