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mTOR inhibition by rapamycin protects against deltamethrin-induced apoptosis in PC12 Cells.
Environ Toxicol. 2017 Jan; 32(1):109-121.ET

Abstract

The autophagy pathway can be induced and upregulated in response to intracellular reactive oxygen species (ROS). In this study, we explored a novel pharmacotherapeutic approach involving the regulation of autophagy to prevent deltamethrin (DLM) neurotoxicity. We found that DLM-induced apoptosis in PC12 cells, as demonstrated by the activation of caspase-3 and -9 and by nuclear condensation. DLM treatment significantly decreased dopamine (DA) levels in PC12 cells. In addition, we observed that cells treated with DLM underwent autophagic cell death, by monitoring the expression of LC3-II, p62, and Beclin-1. Exposure of PC12 cells to DLM led to the production of ROS. Treatment with N-acetyl cysteine (NAC) effectively blocked both apoptosis and autophagy. In addition, mitogen-activated protein kinase (MAPK) inhibitors attenuated apoptosis as well as autophagic cell death. We also investigated the modulation of DLM-induced apoptosis in response to autophagy regulation. Pretreatment with the autophagy inducer, rapamycin, significantly enhanced the viability of DLM-exposed cells, and this enhancement of cell viability was partially due to alleviation of DLM-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), significantly increased DLM toxicity in these cells. Our results suggest that DLM-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against DLM-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 109-121, 2017.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Hanyang University, Korea. Hanyang Biomedical Research Institute, Seoul, Republic of Korea. Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.Department of Pharmacology, College of Medicine, Hanyang University, Korea. Hanyang Biomedical Research Institute, Seoul, Republic of Korea. Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.Department of Pharmacology, College of Medicine, Hanyang University, Korea. Hanyang Biomedical Research Institute, Seoul, Republic of Korea.Department of Pharmacology, College of Medicine, Hanyang University, Korea. Hanyang Biomedical Research Institute, Seoul, Republic of Korea.Department of Pharmacology, College of Medicine, Hanyang University, Korea. Hanyang Biomedical Research Institute, Seoul, Republic of Korea. Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26588882

Citation

Park, Yun Sun, et al. "MTOR Inhibition By Rapamycin Protects Against Deltamethrin-induced Apoptosis in PC12 Cells." Environmental Toxicology, vol. 32, no. 1, 2017, pp. 109-121.
Park YS, Park JH, Ko J, et al. MTOR inhibition by rapamycin protects against deltamethrin-induced apoptosis in PC12 Cells. Environ Toxicol. 2017;32(1):109-121.
Park, Y. S., Park, J. H., Ko, J., Shin, I. C., & Koh, H. C. (2017). MTOR inhibition by rapamycin protects against deltamethrin-induced apoptosis in PC12 Cells. Environmental Toxicology, 32(1), 109-121. https://doi.org/10.1002/tox.22216
Park YS, et al. MTOR Inhibition By Rapamycin Protects Against Deltamethrin-induced Apoptosis in PC12 Cells. Environ Toxicol. 2017;32(1):109-121. PubMed PMID: 26588882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - mTOR inhibition by rapamycin protects against deltamethrin-induced apoptosis in PC12 Cells. AU - Park,Yun Sun, AU - Park,Jae Hyeon, AU - Ko,Juyeon, AU - Shin,In Chul, AU - Koh,Hyun Chul, Y1 - 2015/11/21/ PY - 2015/08/10/received PY - 2015/10/21/revised PY - 2015/11/01/accepted PY - 2015/11/22/pubmed PY - 2017/3/3/medline PY - 2015/11/22/entrez KW - apoptosis KW - autophagy KW - deltamethrin KW - neuroprotection KW - rapamycin SP - 109 EP - 121 JF - Environmental toxicology JO - Environ. Toxicol. VL - 32 IS - 1 N2 - The autophagy pathway can be induced and upregulated in response to intracellular reactive oxygen species (ROS). In this study, we explored a novel pharmacotherapeutic approach involving the regulation of autophagy to prevent deltamethrin (DLM) neurotoxicity. We found that DLM-induced apoptosis in PC12 cells, as demonstrated by the activation of caspase-3 and -9 and by nuclear condensation. DLM treatment significantly decreased dopamine (DA) levels in PC12 cells. In addition, we observed that cells treated with DLM underwent autophagic cell death, by monitoring the expression of LC3-II, p62, and Beclin-1. Exposure of PC12 cells to DLM led to the production of ROS. Treatment with N-acetyl cysteine (NAC) effectively blocked both apoptosis and autophagy. In addition, mitogen-activated protein kinase (MAPK) inhibitors attenuated apoptosis as well as autophagic cell death. We also investigated the modulation of DLM-induced apoptosis in response to autophagy regulation. Pretreatment with the autophagy inducer, rapamycin, significantly enhanced the viability of DLM-exposed cells, and this enhancement of cell viability was partially due to alleviation of DLM-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), significantly increased DLM toxicity in these cells. Our results suggest that DLM-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against DLM-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 109-121, 2017. SN - 1522-7278 UR - https://www.unboundmedicine.com/medline/citation/26588882/mTOR_inhibition_by_rapamycin_protects_against_deltamethrin_induced_apoptosis_in_PC12_Cells_ L2 - https://doi.org/10.1002/tox.22216 DB - PRIME DP - Unbound Medicine ER -