Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells

Irie, Yoshihito; Saeki, Makio; Tanaka, Hidekazu; Kanemura, Yonehiro; Otake, Shinpei; Ozono, Yoshiyuki; Nagai, Toshikazu; Kondo, Yukiko; Kudo, Kazuhiko; Kamisaki, Yoshínori; Miki, Naomasa; Taira, Eiichi

doi:10.1007/s00441-011-1207-5

Cited by 17 publications

(10 citation statements)

References 46 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of misfolded proteins in the ER triggers a cellular stress response called the UPR (Forman et al, 2003; Rutkowski and Kaufman, 2004; Hoozemans et al, 2005; Irie et al, 2011). The protein level of BiP/GRP78, a molecular chaperone which is up-regulated during the UPR, and can be used as a marker of ER stress (Forman et al, 2003; Moreno and Tiffany-Castiglioni, 2015; Casas, 2017; Shimizu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling Pathway

Huang

Tai

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant. METH exposure causes detrimental effects on multiple organ systems, primarily the nervous system, especially dopaminergic pathways, in both laboratory animals and humans. In this study, we hypothesized that Nuclear protein 1 (Nupr1/com1/p8) is involved in METH-induced neuronal apoptosis and autophagy through endoplasmic reticulum (ER) stress signaling pathway. To test this hypothesis, we measured the expression levels of Nupr1, ER stress protein markers CHOP and Trib3, apoptosis-related protein markers cleaved-caspase3 and PARP, as well as autophagy-related protein markers LC3 and Beclin-1 in brain tissues of adult male Sprague-Dawley (SD) rats, rat primary cultured neurons and the rat adrenal pheochromocytoma cells (PC12 cells) after METH exposure. We also determined the effects of METH exposure on the expression of these proteins after silencing Nupr1, CHOP, or Trib3 expression with synthetic small hairpin RNA (shRNA) or siRNA in vitro, and after silencing Nupr1 in the striatum of rats by injecting lentivirus containing shRNA sequence targeting Nupr1 gene to rat striatum. The results showed that METH exposure increased Nupr1 expression that was accompanied with increased expression of ER stress protein markers CHOP and Trib3, and also led to apoptosis and autophagy in rat primary neurons and in PC12 cells after 24 h exposure (3.0 mM), and in the prefrontal cortex and striatum of rats after repeated intraperitoneal injections (15 mg/kg × 8 injections at 12 h intervals). Silencing of Nupr1 expression partly reduced METH-induced apoptosis and autophagy in vitro and in vivo. These results suggest that Nupr1 plays an essential role in METH-caused neuronal apoptosis and autophagy at relatively higher doses and may be a potential therapeutic target in high-dose METH-induced neurotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling Pathway

Huang

Tai

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The neurotoxic mechanism of METH is complex and involves multiple pathways (Ceccatelli, 2013; Shin et al, 2017). METH intake elicits a massive release of dopamine (DA) and excessive glutamate production in the brain, generating a large amount of reactive oxygen species (ROS), and subsequently leading to mitochondrial dysfunction and endoplasmic reticulum (ER) stress (Beauvais et al, 2011; Irie et al, 2011; Dang et al, 2018; Shin et al, 2018). METH has been shown to significantly increase the Bax/Bcl-2 ratio and to disrupt the potential of mitochondrial membranes, triggering a caspase cascade (Jayanthi et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…METH has been shown to significantly increase the Bax/Bcl-2 ratio and to disrupt the potential of mitochondrial membranes, triggering a caspase cascade (Jayanthi et al, 2001). METH also increases the detachment of the major chaperone protein from the transmembrane ER signaling protein glucose-related protein 78 (GRP78) and induces apoptosis by escalating the level of the CCAAT/enhancer-binding protein homologous protein (CHOP) (Irie et al, 2011; Takeichi et al, 2012). In addition, microglial activation and METH-mediated neuroinflammation also contribute to neurotoxicity by attacking the neuron with inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 (Coelho-Santos et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment

et al. 2019

View full text Add to dashboard Cite

Methamphetamine (METH) is a highly addictive stimulant, and METH exposure can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. The ever-increasing levels of METH abuse worldwide have necessitated the identification of effective intervention strategies to protect the brain against METH-induced neurotoxicity. The protective effects of molecular hydrogen on oxidative stress and related neurodegenerative diseases have been recently elucidated. Herein, we investigated whether treatment with molecular hydrogen ameliorated the METH-induced neurotoxicity and spatial learning and memory impairments. Male C57BL/6 mice received four intraperitoneal METH injections (10 mg/kg, 3-h interval), and stereotypic behaviors and hyperthermia were observed. After METH treatment and behavioral observation, the mice were returned to their home cages, where they received water or hydrogen-rich water (HRW) ad libitum for 7 days. We found that the molecular hydrogen delivered by ad libitum HRW consumption significantly inhibited the METH-induced spatial learning impairment and memory loss evidenced in the Barnes maze and Morris water maze tests. Furthermore, molecular hydrogen significantly restrained the neuronal damage in the hippocampus after high-dose METH exposure. Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the hippocampus. These are the first findings to indicate that hydrogen might ameliorate METH-induced neurotoxicity and has a potential application in reducing the risk of neurodegeneration frequently observed in METH abusers.

show abstract

“…The most studied key downstream event is apoptotic cell death (Irie et al, 2011;Kanthasamy et al, 2006;Kongsuphol et al, 2009;Nopparat et al, 2010;Pitaksalee et al, 2015;Shivalingappa et al, 2012;Suwanjang et al, 2010;Wu et al, 2014;Xuan-Khanh Thi et al, 2015), and ER stress (Irie et al, 2011) as well as activation of JNK (Nopparat et al, 2010) have been implicated as preceding events to apoptotic cell death.…”

Section: Supporting Publications 2016: En-955 77mentioning

confidence: 99%

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Choi¹,

Polcher²,

Joas³

2016

EFSA Supporting Publications

View full text Add to dashboard Cite

This report presents the outcomes of a systematic review (SR) identifying the mechanisms and chemicals involved in the pathogenesis of Parkinson's disease (PD) and childhood leukaemia (CL). This work serves as a basis for defining and mapping the causal linkages between a molecular initiating event (MIE) and a final adverse outcome (AO) that are relevant for the development of a prototype adverse outcome pathway (AOP) for assessing risk factors for PD and CL. Search for literature from 1990 to present was conducted using Web of Science, PubMed and TOXNET, and relevant references were selected using established inclusion/exclusion criteria and ranked using a set of quality control factors.For PD, 7,384 individual references were identified to be relevant for PD pathogenesis and chemicals associated with PD. Dopaminergic neurodegeneration in the substantia nigra leading to locomotor deficits was identified as the AO in PD. Other identified key events in PD pathogenesis include mitochondrial dysfunction, cellular accumulation of alpha-synuclein and oxidative stress. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and paraquat are some chemicals identified to be associated with PD pathogenesis.For CL, 1,988 individual references were identified to be relevant for CL pathogenesis and chemicals associated with CL. Chromosomal translocation, genetic damage/mutation and hyperdiploidy are considered as driving forces of CL. Except for infant leukaemia, CL pathogenesis requires a 'two-hit' model with an initiating event occurring in utero followed by a secondary hit potentially occurring after birth. Potential MIEs leading to these driving mechanisms include aberrant DNA topoisomerase II activity and erroneous DNA repair. Epigenetics appears to also play an influential role in CL pathogenesis. Benzene, bioflavonoids and organophosphates are some chemicals identified to be implicated in CL pathogenesis.The challenges of developing AOPs for these two diseases and the data gaps identified from the outcomes of this SR are also elaborated in this report. The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. KEY WORDSSystematic Review, Parkinson Disease, Childhood Leukaemia, Pathogenesis, Chemicals, Pesticides, Adverse Outcome Pathway SUMMARYThe aim of this project was to perform a systematic review (SR) to collect relevant publications related to the mechanisms involved in the pathogenesis of Parkinson's disease (PD)...

show abstract

Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells

Cited by 17 publications

References 46 publications

Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling Pathway

Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling Pathway

Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Contact Info

Product

Resources

About