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Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines.
J Toxicol Sci. 2017; 42(1):63-71.JT

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, Faculty of Medical Science Naresuan University, Thailand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28070110

Citation

Tungkum, Wanida, et al. "Melatonin Suppresses Methamphetamine-triggered Endoplasmic Reticulum Stress in C6 Cells Glioma Cell Lines." The Journal of Toxicological Sciences, vol. 42, no. 1, 2017, pp. 63-71.
Tungkum W, Jumnongprakhon P, Tocharus C, et al. Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines. J Toxicol Sci. 2017;42(1):63-71.
Tungkum, W., Jumnongprakhon, P., Tocharus, C., Govitrapong, P., & Tocharus, J. (2017). Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines. The Journal of Toxicological Sciences, 42(1), 63-71. https://doi.org/10.2131/jts.42.63
Tungkum W, et al. Melatonin Suppresses Methamphetamine-triggered Endoplasmic Reticulum Stress in C6 Cells Glioma Cell Lines. J Toxicol Sci. 2017;42(1):63-71. PubMed PMID: 28070110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines. AU - Tungkum,Wanida, AU - Jumnongprakhon,Pichaya, AU - Tocharus,Chainarong, AU - Govitrapong,Piyarat, AU - Tocharus,Jiraporn, PY - 2017/1/11/entrez PY - 2017/1/11/pubmed PY - 2017/5/24/medline SP - 63 EP - 71 JF - The Journal of toxicological sciences JO - J Toxicol Sci VL - 42 IS - 1 N2 - 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. SN - 1880-3989 UR - https://www.unboundmedicine.com/medline/citation/28070110/Melatonin_suppresses_methamphetamine_triggered_endoplasmic_reticulum_stress_in_C6_cells_glioma_cell_lines_ L2 - https://dx.doi.org/10.2131/jts.42.63 DB - PRIME DP - Unbound Medicine ER -