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Lupenone Protects Neuroblastoma SH-SY5y Cells Against Methamphetamine-Induced Apoptotic Cell Death via PI3K/Akt/mTOR Signaling Pathway.
Int J Mol Sci. 2020 Feb 27; 21(5)IJ

Abstract

Methamphetamine (METH) is an addictive psychostimulant showing neurotoxicity through neuronal apoptosis and the neuro-inflammatory pathway. Lupenone, a lupane triterpenoid, is an isolated compound exhibiting anti-oxidative, anti-inflammation, and anti-diabetic activities. However, whether lupenone plays a protective role against apoptosis induced by METH in SH-SY5y neuroblastoma cells remains unknown. In the present study, we elucidated that lupenone had no toxicity to SH-SY5y cells at different concentrations. On the other hand, we found that the treatment of SH-SY5y cells with an optimal concentration of lupenone could lead to protection against cell death induced by METH. AnnexinV/PI apoptosis analysis revealed a dramatically reduced level of the apoptotic cell population in lupenon and METH treated SH-SY5y cells. Moreover, diminished expression of anti-apoptotic proteins, including Bcl-2, Caspase3, Caspase7, and Caspase8 in METH-exposed SH-SY5y cells, was significantly recovered by treatment with lupenone. This protection in the expression of anti-apoptotic proteins was due to an increased phosphorylation level of PI3K/Akt in METH-treated SH-SY5y cells pre-incubated with lupenone. These findings suggest that lupenone can protect SH-SY5y cells against METH-induced neuronal apoptosis through the PI3K/Akt 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

32120831

Citation

Lee, Hyun-Su, et al. "Lupenone Protects Neuroblastoma SH-SY5y Cells Against Methamphetamine-Induced Apoptotic Cell Death Via PI3K/Akt/mTOR Signaling Pathway." International Journal of Molecular Sciences, vol. 21, no. 5, 2020.
Lee HS, Kim EN, Jeong GS. Lupenone Protects Neuroblastoma SH-SY5y Cells Against Methamphetamine-Induced Apoptotic Cell Death via PI3K/Akt/mTOR Signaling Pathway. Int J Mol Sci. 2020;21(5).
Lee, H. S., Kim, E. N., & Jeong, G. S. (2020). Lupenone Protects Neuroblastoma SH-SY5y Cells Against Methamphetamine-Induced Apoptotic Cell Death via PI3K/Akt/mTOR Signaling Pathway. International Journal of Molecular Sciences, 21(5). https://doi.org/10.3390/ijms21051617
Lee HS, Kim EN, Jeong GS. Lupenone Protects Neuroblastoma SH-SY5y Cells Against Methamphetamine-Induced Apoptotic Cell Death Via PI3K/Akt/mTOR Signaling Pathway. Int J Mol Sci. 2020 Feb 27;21(5) PubMed PMID: 32120831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lupenone Protects Neuroblastoma SH-SY5y Cells Against Methamphetamine-Induced Apoptotic Cell Death via PI3K/Akt/mTOR Signaling Pathway. AU - Lee,Hyun-Su, AU - Kim,Eun-Nam, AU - Jeong,Gil-Saeng, Y1 - 2020/02/27/ PY - 2019/12/12/received PY - 2020/02/17/revised PY - 2020/02/25/accepted PY - 2020/3/4/entrez PY - 2020/3/4/pubmed PY - 2020/3/4/medline KW - Akt KW - PI3K KW - apoptosis KW - methamphetamine KW - neuroblastoma JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 5 N2 - Methamphetamine (METH) is an addictive psychostimulant showing neurotoxicity through neuronal apoptosis and the neuro-inflammatory pathway. Lupenone, a lupane triterpenoid, is an isolated compound exhibiting anti-oxidative, anti-inflammation, and anti-diabetic activities. However, whether lupenone plays a protective role against apoptosis induced by METH in SH-SY5y neuroblastoma cells remains unknown. In the present study, we elucidated that lupenone had no toxicity to SH-SY5y cells at different concentrations. On the other hand, we found that the treatment of SH-SY5y cells with an optimal concentration of lupenone could lead to protection against cell death induced by METH. AnnexinV/PI apoptosis analysis revealed a dramatically reduced level of the apoptotic cell population in lupenon and METH treated SH-SY5y cells. Moreover, diminished expression of anti-apoptotic proteins, including Bcl-2, Caspase3, Caspase7, and Caspase8 in METH-exposed SH-SY5y cells, was significantly recovered by treatment with lupenone. This protection in the expression of anti-apoptotic proteins was due to an increased phosphorylation level of PI3K/Akt in METH-treated SH-SY5y cells pre-incubated with lupenone. These findings suggest that lupenone can protect SH-SY5y cells against METH-induced neuronal apoptosis through the PI3K/Akt pathway. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32120831/Lupenone_Protects_Neuroblastoma_SH_SY5y_Cells_Against_Methamphetamine_Induced_Apoptotic_Cell_Death_via_PI3K/Akt/mTOR_Signaling_Pathway_ L2 - https://www.mdpi.com/resolver?pii=ijms21051617 DB - PRIME DP - Unbound Medicine ER -