Tacrine induces endoplasmic reticulum-stressed apoptosis via disrupting the proper assembly of oligomeric acetylcholinesterase in cultured 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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Phenylbutyric Acid Rescues Endoplasmic Reticulum Stress-Induced Suppression of APP Proteolysis and Prevents Apoptosis in Neuronal Cells

PLoS ONE ◽

10.1371/journal.pone.0009135 ◽

2010 ◽

Vol 5 (2) ◽

pp. e9135 ◽

Cited By ~ 47

Author(s):

Jesse C. Wiley ◽

James S. Meabon ◽

Harald Frankowski ◽

Elise A. Smith ◽

Leslayann C. Schecterson ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Neuronal Cells ◽

Phenylbutyric Acid

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Methamphetamine induces GSDME-dependent cell death in hippocampal neuronal cells through the endoplasmic reticulum stress pathway

Brain Research Bulletin ◽

10.1016/j.brainresbull.2020.06.005 ◽

2020 ◽

Vol 162 ◽

pp. 73-83

Author(s):

Yi Liu ◽

Di Wen ◽

Jingqi Gao ◽

Bing Xie ◽

Hailei Yu ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Cell Death ◽

Endoplasmic Reticulum Stress ◽

Neuronal Cells ◽

Dependent Cell ◽

Endoplasmic Reticulum Stress Pathway ◽

Stress Pathway

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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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