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PPAR-γ activation attenuates deltamethrin-induced apoptosis by regulating cytosolic PINK1 and inhibiting mitochondrial dysfunction.
Toxicol Lett. 2016 Oct 17; 260:8-17.TL

Abstract

Central events in the mitochondrial-dependent cell death pathway include the disruption of mitochondrial membrane potential, which causes the release of apoptogenic molecules leading to cell death. Based on the cytotoxic mechanism of deltamethrin (DLM), we examined the neuroprotective mechanisms of rosiglitazone (RGZ), which is against DLM-induced neuronal cell death. In this study, we found that DLM induces apoptosis in SH-SY5Y cells as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, neuronal cell death in response to DLM was due to mitochondrial dependent-apoptosis pathways since DLM increased cytochrome c release into the cytosol and activated caspase-9. DLM exposure reduced PINK1 expression, and pretreatment with RGZ significantly reduced cytochrome c release and caspase-9 activation. RGZ also attenuated the reduction of complex I activity, mitochondrial membrane potential, and ATP levels. Pretreatment with RGZ significantly enhanced PINK1 expression in DLM-exposed cells. In addition, RGZ increased cytosolic PINK1 by inhibiting mitochondrial translocation of PINK1. Interestingly, RGZ fails to rescue DLM-induced mitochondrial dysfunction both in PINK1 knockdown and PPAR-γ antagonist treated cells. Results from this study suggest that RGZ exerts anti-apoptotic effects against DLM-induced cytotoxicity by attenuation of mitochondrial dysfunction through cytosolic PINK1-dependent signaling pathways.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, 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.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, 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. Electronic address: hckoh@hanyang.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27553674

Citation

Ko, Juyeon, et al. "PPAR-γ Activation Attenuates Deltamethrin-induced Apoptosis By Regulating Cytosolic PINK1 and Inhibiting Mitochondrial Dysfunction." Toxicology Letters, vol. 260, 2016, pp. 8-17.
Ko J, Park JH, Park YS, et al. PPAR-γ activation attenuates deltamethrin-induced apoptosis by regulating cytosolic PINK1 and inhibiting mitochondrial dysfunction. Toxicol Lett. 2016;260:8-17.
Ko, J., Park, J. H., Park, Y. S., & Koh, H. C. (2016). PPAR-γ activation attenuates deltamethrin-induced apoptosis by regulating cytosolic PINK1 and inhibiting mitochondrial dysfunction. Toxicology Letters, 260, 8-17. https://doi.org/10.1016/j.toxlet.2016.08.016
Ko J, et al. PPAR-γ Activation Attenuates Deltamethrin-induced Apoptosis By Regulating Cytosolic PINK1 and Inhibiting Mitochondrial Dysfunction. Toxicol Lett. 2016 Oct 17;260:8-17. PubMed PMID: 27553674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PPAR-γ activation attenuates deltamethrin-induced apoptosis by regulating cytosolic PINK1 and inhibiting mitochondrial dysfunction. AU - Ko,Juyeon, AU - Park,Jae Hyeon, AU - Park,Yun Sun, AU - Koh,Hyun Chul, Y1 - 2016/08/21/ PY - 2016/06/14/received PY - 2016/08/16/revised PY - 2016/08/19/accepted PY - 2016/8/25/pubmed PY - 2017/1/31/medline PY - 2016/8/25/entrez KW - Apoptosis KW - Deltamethrin KW - Mitochondrial dysfunction KW - PINK1 KW - Rosiglitazone SP - 8 EP - 17 JF - Toxicology letters JO - Toxicol. Lett. VL - 260 N2 - Central events in the mitochondrial-dependent cell death pathway include the disruption of mitochondrial membrane potential, which causes the release of apoptogenic molecules leading to cell death. Based on the cytotoxic mechanism of deltamethrin (DLM), we examined the neuroprotective mechanisms of rosiglitazone (RGZ), which is against DLM-induced neuronal cell death. In this study, we found that DLM induces apoptosis in SH-SY5Y cells as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, neuronal cell death in response to DLM was due to mitochondrial dependent-apoptosis pathways since DLM increased cytochrome c release into the cytosol and activated caspase-9. DLM exposure reduced PINK1 expression, and pretreatment with RGZ significantly reduced cytochrome c release and caspase-9 activation. RGZ also attenuated the reduction of complex I activity, mitochondrial membrane potential, and ATP levels. Pretreatment with RGZ significantly enhanced PINK1 expression in DLM-exposed cells. In addition, RGZ increased cytosolic PINK1 by inhibiting mitochondrial translocation of PINK1. Interestingly, RGZ fails to rescue DLM-induced mitochondrial dysfunction both in PINK1 knockdown and PPAR-γ antagonist treated cells. Results from this study suggest that RGZ exerts anti-apoptotic effects against DLM-induced cytotoxicity by attenuation of mitochondrial dysfunction through cytosolic PINK1-dependent signaling pathways. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/27553674/PPAR_γ_activation_attenuates_deltamethrin_induced_apoptosis_by_regulating_cytosolic_PINK1_and_inhibiting_mitochondrial_dysfunction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(16)33118-6 DB - PRIME DP - Unbound Medicine ER -