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Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway.
Toxicol In Vitro. 2018 Feb; 46:58-65.TV

Abstract

Paraquat (PQ), as one of the most widely used herbicides in the world, can cause severe lung damage in humans and animals. This study investigated the underlying molecular mechanism of PQ-induced lung cell damage and the protective role of salubrinal. Human lung epithelial-like A549 cells were treated with PQ for 24h and were pre-incubated with salubrinal for 2h, followed by 500μM of PQ treatment. Silencing eIF2α gene of the A549 cells with siRNA interference method was conducted. Cell morphology, cell viability, apoptosis and caspase-3 activity were assessed by different assays accordingly thereafter. The expression of PERK, p-PERK, ATF6, c-ATF6, IRE1α, p-IRE1α, CHOP, GRP78, p-eIF2α and β-actin was assayed by western blot. The data showed that PQ significantly reduced A549 cell viability, changed cell morphology, induced cell apoptosis and significantly upregulated the levels of GRP78, CHOP, p-PERK, c-ATF6 and p-IRE1α. However, 30μM salubrinal could attenuate the effects of PQ on damages to A549 cells through upregulating p-eIF2α. In contrast, knocking down eIF2α gene inhabited the effects of salubrinal. These results suggest that PQ-induced A549 cell apoptosis involved endoplasmic reticulum (ER) stress, specially the PERK-eIF2α pathway. Salubrinal attenuated A549 cells from PQ-induced damages through regulation of the PERK-eIF2α signaling.

Authors+Show Affiliations

Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China. Electronic address: sxying8655@sina.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28986289

Citation

Wang, Rui, et al. "Eukaryotic Translation Initiation Factor 2 Subunit Α (eIF2α) Inhibitor Salubrinal Attenuates Paraquat-induced Human Lung Epithelial-like A549 Cell Apoptosis By Regulating the PERK-eIF2α Signaling Pathway." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 46, 2018, pp. 58-65.
Wang R, Sun DZ, Song CQ, et al. Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway. Toxicol In Vitro. 2018;46:58-65.
Wang, R., Sun, D. Z., Song, C. Q., Xu, Y. M., Liu, W., Liu, Z., & Dong, X. S. (2018). Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 46, 58-65. https://doi.org/10.1016/j.tiv.2017.10.006
Wang R, et al. Eukaryotic Translation Initiation Factor 2 Subunit Α (eIF2α) Inhibitor Salubrinal Attenuates Paraquat-induced Human Lung Epithelial-like A549 Cell Apoptosis By Regulating the PERK-eIF2α Signaling Pathway. Toxicol In Vitro. 2018;46:58-65. PubMed PMID: 28986289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway. AU - Wang,Rui, AU - Sun,Da-Zhuang, AU - Song,Chun-Qing, AU - Xu,Yong-Min, AU - Liu,Wei, AU - Liu,Zhi, AU - Dong,Xue-Song, Y1 - 2017/10/03/ PY - 2017/03/18/received PY - 2017/08/16/revised PY - 2017/10/02/accepted PY - 2017/10/8/pubmed PY - 2018/7/22/medline PY - 2017/10/8/entrez KW - Apoptosis KW - Endoplasmic reticulum stress KW - PERK KW - Paraquat KW - Salubrinal KW - eIF2α inhibitor SP - 58 EP - 65 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 46 N2 - Paraquat (PQ), as one of the most widely used herbicides in the world, can cause severe lung damage in humans and animals. This study investigated the underlying molecular mechanism of PQ-induced lung cell damage and the protective role of salubrinal. Human lung epithelial-like A549 cells were treated with PQ for 24h and were pre-incubated with salubrinal for 2h, followed by 500μM of PQ treatment. Silencing eIF2α gene of the A549 cells with siRNA interference method was conducted. Cell morphology, cell viability, apoptosis and caspase-3 activity were assessed by different assays accordingly thereafter. The expression of PERK, p-PERK, ATF6, c-ATF6, IRE1α, p-IRE1α, CHOP, GRP78, p-eIF2α and β-actin was assayed by western blot. The data showed that PQ significantly reduced A549 cell viability, changed cell morphology, induced cell apoptosis and significantly upregulated the levels of GRP78, CHOP, p-PERK, c-ATF6 and p-IRE1α. However, 30μM salubrinal could attenuate the effects of PQ on damages to A549 cells through upregulating p-eIF2α. In contrast, knocking down eIF2α gene inhabited the effects of salubrinal. These results suggest that PQ-induced A549 cell apoptosis involved endoplasmic reticulum (ER) stress, specially the PERK-eIF2α pathway. Salubrinal attenuated A549 cells from PQ-induced damages through regulation of the PERK-eIF2α signaling. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/28986289/Eukaryotic_translation_initiation_factor_2_subunit_α__eIF2α__inhibitor_salubrinal_attenuates_paraquat_induced_human_lung_epithelial_like_A549_cell_apoptosis_by_regulating_the_PERK_eIF2α_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(17)30288-6 DB - PRIME DP - Unbound Medicine ER -