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Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway.
Int J Mol Sci. 2021 Feb 25; 22(5)IJ

Abstract

Methamphetamine (METH) is a highly addictive drug that induces irreversible damage to neuronal cells and pathological malfunction in the brain. Aromadendrin, isolated from the flowers of Chionanthus retusus, has been shown to have anti-inflammatory or anti-tumor activity. Nevertheless, it has been reported that METH exacerbates neurotoxicity by inducing endoplasmic reticulum (ER) stress via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in neuronal cells. There is little evidence that aromadendrin protects cells from neurotoxicity induced by METH. In this study, we found that aromadendrin partially suppressed the METH-induced cell death in SH-SY5y cells without causing cytotoxicity. Aromadendrin regulated METH-induced ER stress by preserving the phosphorylation of the PI3K/Akt/mTOR signaling pathway in METH-exposed SH-SY5y cells. In addition, aromadendrin mitigated METH-induced autophagic and the apoptotic pathways in METH-exposed SH-SY5y cells. Mechanistic studies revealed that pre-treatment with aromadendrin restored the expression of anti-apoptotic proteins in METH-exposed conditions. The inhibitor assay confirmed that aromadendrin-mediated restoration of mTOR phosphorylation protected cells from autophagy and apoptosis in METH-exposed cells. Therefore, these findings suggest that aromadendrin relatively has a protective effect on SH-SY5y cells against autophagy and apoptosis induced by METH via regulation of ER stress and the PI3K/Akt/mTOR signaling pathway.

Authors+Show Affiliations

College of Pharmacy, Keimyung University, Daegu 42601, Korea.College of Pharmacy, Keimyung University, Daegu 42601, Korea.College of Pharmacy, Keimyung University, Daegu 42601, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33668860

Citation

Lee, Hyun-Su, et al. "Aromadendrin Protects Neuronal Cells From Methamphetamine-Induced Neurotoxicity By Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway." International Journal of Molecular Sciences, vol. 22, no. 5, 2021.
Lee HS, Kim EN, Jeong GS. Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway. Int J Mol Sci. 2021;22(5).
Lee, H. S., Kim, E. N., & Jeong, G. S. (2021). Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway. International Journal of Molecular Sciences, 22(5). https://doi.org/10.3390/ijms22052274
Lee HS, Kim EN, Jeong GS. Aromadendrin Protects Neuronal Cells From Methamphetamine-Induced Neurotoxicity By Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway. Int J Mol Sci. 2021 Feb 25;22(5) PubMed PMID: 33668860.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway. AU - Lee,Hyun-Su, AU - Kim,Eun-Nam, AU - Jeong,Gil-Saeng, Y1 - 2021/02/25/ PY - 2021/01/10/received PY - 2021/02/13/revised PY - 2021/02/22/accepted PY - 2021/3/6/entrez PY - 2021/3/7/pubmed PY - 2021/4/17/medline KW - METH KW - SH-SY5y cells KW - aromadendrin KW - mTOR signaling KW - neurotoxicity KW - protection JF - International journal of molecular sciences JO - Int J Mol Sci VL - 22 IS - 5 N2 - Methamphetamine (METH) is a highly addictive drug that induces irreversible damage to neuronal cells and pathological malfunction in the brain. Aromadendrin, isolated from the flowers of Chionanthus retusus, has been shown to have anti-inflammatory or anti-tumor activity. Nevertheless, it has been reported that METH exacerbates neurotoxicity by inducing endoplasmic reticulum (ER) stress via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in neuronal cells. There is little evidence that aromadendrin protects cells from neurotoxicity induced by METH. In this study, we found that aromadendrin partially suppressed the METH-induced cell death in SH-SY5y cells without causing cytotoxicity. Aromadendrin regulated METH-induced ER stress by preserving the phosphorylation of the PI3K/Akt/mTOR signaling pathway in METH-exposed SH-SY5y cells. In addition, aromadendrin mitigated METH-induced autophagic and the apoptotic pathways in METH-exposed SH-SY5y cells. Mechanistic studies revealed that pre-treatment with aromadendrin restored the expression of anti-apoptotic proteins in METH-exposed conditions. The inhibitor assay confirmed that aromadendrin-mediated restoration of mTOR phosphorylation protected cells from autophagy and apoptosis in METH-exposed cells. Therefore, these findings suggest that aromadendrin relatively has a protective effect on SH-SY5y cells against autophagy and apoptosis induced by METH via regulation of ER stress and the PI3K/Akt/mTOR signaling pathway. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/33668860/Aromadendrin_Protects_Neuronal_Cells_from_Methamphetamine_Induced_Neurotoxicity_by_Regulating_Endoplasmic_Reticulum_Stress_and_PI3K/Akt/mTOR_Signaling_Pathway_ L2 - https://www.mdpi.com/resolver?pii=ijms22052274 DB - PRIME DP - Unbound Medicine ER -