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Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells.
Toxicol Lett. 2013 Oct 23; 223(1):25-34.TL

Abstract

Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24008047

Citation

Park, Jae Hyeon, et al. "Potential Autophagy Enhancers Protect Against Fipronil-induced Apoptosis in SH-SY5Y Cells." Toxicology Letters, vol. 223, no. 1, 2013, pp. 25-34.
Park JH, Lee JE, Lee SJ, et al. Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells. Toxicol Lett. 2013;223(1):25-34.
Park, J. H., Lee, J. E., Lee, S. J., Park, S. J., Park, K. H., Jeong, M., & Koh, H. C. (2013). Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells. Toxicology Letters, 223(1), 25-34. https://doi.org/10.1016/j.toxlet.2013.08.015
Park JH, et al. Potential Autophagy Enhancers Protect Against Fipronil-induced Apoptosis in SH-SY5Y Cells. Toxicol Lett. 2013 Oct 23;223(1):25-34. PubMed PMID: 24008047.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells. AU - Park,Jae Hyeon, AU - Lee,Jeong Eun, AU - Lee,Soo-Jin, AU - Park,Soo Jin, AU - Park,Kyung Hun, AU - Jeong,Mihye, AU - Koh,Hyun Chul, Y1 - 2013/09/02/ PY - 2013/06/24/received PY - 2013/08/20/revised PY - 2013/08/21/accepted PY - 2013/9/7/entrez PY - 2013/9/7/pubmed PY - 2014/3/29/medline KW - Apoptosis KW - Autophagy KW - Fipronil KW - Neuroprotection KW - Rapamycin KW - Reactive oxygen species SP - 25 EP - 34 JF - Toxicology letters JO - Toxicol. Lett. VL - 223 IS - 1 N2 - Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/24008047/Potential_autophagy_enhancers_protect_against_fipronil_induced_apoptosis_in_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(13)01287-3 DB - PRIME DP - Unbound Medicine ER -