Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines
-
- Tungkum Wanida
- Department of Biochemistry, Faculty of Medical Science Naresuan University, Thailand
-
- Jumnongprakhon Pichaya
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Thailand
-
- Tocharus Chainarong
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Thailand
-
- Govitrapong Piyarat
- Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Thailand Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Thailand
-
- Tocharus Jiraporn
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Thailand
Search this article
Abstract
<p>Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood. This study investigated the protective effect of melatonin against METH toxicity-mediated ER stress in glial cells. Our study demonstrated that METH increased glial cell toxicity related to METH-induced ER stress by stimulating the unfolded protein response (UPR) to activate the expression of ER stress transducers, including phosphorylated double-stranded RNA-activated protein kinase (PKR)-like ER kinase (p-PERK), activating transcription factor (ATF6), and phosphorylated inositol-requiring enzyme 1 (p-IRE1). Moreover, the expression of binding immunoglobulin protein (Bip), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, phosphorylated eukaryotic translation initiation factor 2 alpha (p-eIF2α) and spliced X-box-binding protein-1 (XBP-1) mRNA were also increased. Melatonin reduced ER stress induced by METH toxicity by reducing the expression of ER stress response genes and proteins in a concentration-dependent manner. In addition, melatonin promoted the expression of Bip chaperone in a concentration-dependent manner. Taken together, our findings suggest that melatonin can protect against ER stress-induced glial cell death induced by METH.</p>
Journal
-
- The Journal of Toxicological Sciences
-
The Journal of Toxicological Sciences 42 (1), 63-71, 2017
The Japanese Society of Toxicology
- Tweet
Details 詳細情報について
-
- CRID
- 1390001204906109184
-
- NII Article ID
- 130005286639
-
- NII Book ID
- AN00002808
-
- ISSN
- 18803989
- 03881350
-
- NDL BIB ID
- 027966476
-
- PubMed
- 28070110
-
- Text Lang
- en
-
- Data Source
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- Abstract License Flag
- Disallowed