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

We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gen...

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Veröffentlicht in:Cell and tissue research 2011-08, Vol.345 (2), p.231-241
Hauptverfasser: Irie, Yasuyuki, Saeki, Makio, Tanaka, Hidekazu, Kanemura, Yonehiro, Otake, Shinpei, Ozono, Yoshiyuki, Nagai, Toshisaburou, Kondo, Yukiko, Kudo, Kenzo, Kamisaki, Yoshinori, Miki, Naomasa, Taira, Eiichi
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container_title Cell and tissue research
container_volume 345
creator Irie, Yasuyuki
Saeki, Makio
Tanaka, Hidekazu
Kanemura, Yonehiro
Otake, Shinpei
Ozono, Yoshiyuki
Nagai, Toshisaburou
Kondo, Yukiko
Kudo, Kenzo
Kamisaki, Yoshinori
Miki, Naomasa
Taira, Eiichi
description We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction.
doi_str_mv 10.1007/s00441-011-1207-5
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Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. 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subjects Addiction
Analysis
Animals
Apoptosis
Biomedical and Life Sciences
Biomedicine
BiP protein
Cell body
Central nervous system
CHOP protein
Dopamine
Dopamine - biosynthesis
Dopamine Agents - pharmacology
Dopaminergic Neurons - drug effects
Dopaminergic Neurons - metabolism
Endoplasmic reticulum
Endoplasmic Reticulum - drug effects
Gene Expression Regulation - drug effects
Genes
Human Genetics
Immunofluorescence
Methamphetamine
Methamphetamine - toxicity
Mice
Microscopy
Molecular Medicine
Nervous system
Neurons
Polymerase chain reaction
Proteins
Proteomics
Receptors, Dopamine D1 - metabolism
Regular
Regular Article
Rodents
Stress
Substantia nigra
Toxicity
Transcription Factor CHOP - biosynthesis
Transcription Factor CHOP - genetics
Ventral tegmentum
title Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells
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