Melatonin attenuates methamphetamine‐induced deactivation of the mammalian target of rapamycin signaling to induce autophagy in SK‐N‐SH cells

Kongsuphol, Patthara; Mukda, Sujira; Nopparat, Chutikorn; Villarroel, Alfredo; Govitrapong, Piyarat

doi:10.1111/j.1600-079x.2008.00648.x

Cited by 82 publications

(61 citation statements)

References 50 publications

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“…MLT has been shown to activate mTOR signaling and prevent ischemic brain injury and methamphetamine-induced neurotoxicity [36,37]. In this study, mTOR activity was decreased in livers subjected to I/R as demonstrated by decreased phosphorylation of mTOR, 4E-BP1 and 70S6K, while MLT treatment attenuated this decrease.…”

Section: Discussionmentioning

confidence: 52%

Melatonin Inhibits mTOR-Dependent Autophagy during Liver Ischemia/Reperfusion

Kang

Cho

Lee

2014

Cell Physiol Biochem

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Background: Autophagy is a self-digestion system responsible for maintaining cellular homeostasis and interacts with reactive oxygen species produced during ischemia/reperfusion (I/R). Melatonin (MLT) is a potent and endogenous anti-oxidant that has beneficial effects in liver I/R injury. In this study, we examined the cytoprotective mechanisms of MLT in liver I/R, focusing on autophagic flux and associated signaling pathways. Methods: Male C57BL/6 mice were subjected to 70% liver ischemia for 60 min followed by reperfusion. MLT (10 mg/kg, i.p.) was injected 15 min prior to ischemia and again immediately before reperfusion. Rapamycin (Rapa, 1 mg/kg, i.p.), which induces autophagy, was injected 1.5 h before ischemia. Results: Liver I/R increased autophagic flux as indicated by the accumulation of LC3-II and degradation of sequestosome1/p62. This increase was attenuated by MLT. Likewise, electron microscopic analysis showed that autophagic vacuoles were increased in livers of mice exposed to I/R, which was attenuated by MLT. I/R decreased phosphorylation of mammalian target of rapamycin (mTOR) and 4E-BP1 and 70S6K, downstream molecules of the mTOR pathway, but increased expression of calpain 1 and calpain 2. MLT attenuated the decrease in mTOR, 4E-BP1 and 70S6K phosphorylation. Pretreatment of Rapa reversed the effect of MLT on autophagic flux as well as mTOR pathway. Conclusion: Our findings suggest that MLT downregulates autophagy via activation of mTOR signaling, which may in turn contribute to its protective effects in liver I/R injury.

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Section: Discussionmentioning

confidence: 52%

Melatonin Inhibits mTOR-Dependent Autophagy during Liver Ischemia/Reperfusion

Kang

Cho

Lee

2014

Cell Physiol Biochem

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“…Previous studies suggest that chronic MA exposure decreases the phosphorylation of GSK3β in the ventral M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 tegmental area [12] and acute amphetamine treatment decreases the phosphorylation of Akt/GSK3 pathway in the striatum [13]. Besides, MA inhibits the activity of mTOR in both PC12 and SK-N-SH cells and the phosphorylation of mTOR is protective against MA induced neurotoxicity [14,15]. However, the effect of MA on Akt/ GSK3β/mTOR pathway in vitro has not been clearly determined yet.…”

Section: Introductionmentioning

confidence: 95%

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Zhu

Zhang

et al. 2015

Biochemical and Biophysical Research Communications

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“…Previous studies have demonstrated that melatonin protected neuronal and glial cells in the central nervous system (CNS) after exposure to METH, both in vivo and in vitro, by reducing both inflammation cytokine production and the death signaling response [31][32][33][34][35][36][37][38][39]. However, the mechanism of inflammation in glial cells has not been extensively studied.…”

Section: Introductionmentioning

confidence: 97%

Melatonin Protects Methamphetamine-Induced Neuroinflammation Through NF-κB and Nrf2 Pathways in Glioma Cell Line

et al. 2015

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Methamphetamine (METH) is known as a toxin for neuronal and glial cells. Previous studies have found that METH-induced glial cell death and inflammation is mediated by oxidative stress. However, the exact mechanisms of the inflammatory response remain unclear. Therefore, we hypothesized that the activation of nuclear factor-κB (NF-κB) signaling, a key mediator of inflammation, and the inhibition of nuclear factor erythroid 2-related factor-2 (Nrf2) signaling, a regulator of the antioxidant response, would be significant events occurring in response to METH-induced inflammation in a rat glioma cell line (C6 cells). Our results show that METH increased the production of nitric oxide (NO) and up-regulated the expression of its main regulatory protein, inducible nitric oxide synthase (iNOS). METH also induced NF-κB activation by increasing inhibitory κBα (IκBα) degradation and translocation of the NF-κB (p65) subunit into the nucleus. Additionally, METH inhibited the activation of the Nrf2 pathway by decreasing the translocation of Nrf2 into the nucleus and also by suppressing the expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO-1), and glutamate-cysteine ligase catalytic subunit (γ-GCLC), resulting in the suppression of superoxide dismutase (SOD) activity. Pretreatment with melatonin effectively promoted Nrf2 activation and reversed the METH-induced NF-κB response. Melatonin increased the expression of HO-1, NQO-1, and γ-GCLC, resulting in increased SOD activity. In addition, melatonin also decreased IκBα degradation, translocation of the p65 subunit, and expression of iNOS, resulting in decreased NO production. Taken together, our results indicate that melatonin diminishes the proinflammatory mediator in METH-stimulated C6 cells by inhibiting NF-κB activation and inducing Nrf2-mediated HO-1, NQO-1, and γ-GCLC expression.

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Melatonin attenuates methamphetamine‐induced deactivation of the mammalian target of rapamycin signaling to induce autophagy in SK‐N‐SH cells

Cited by 82 publications

References 50 publications

Melatonin Inhibits mTOR-Dependent Autophagy during Liver Ischemia/Reperfusion

Melatonin Inhibits mTOR-Dependent Autophagy during Liver Ischemia/Reperfusion

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Melatonin Protects Methamphetamine-Induced Neuroinflammation Through NF-κB and Nrf2 Pathways in Glioma Cell Line

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