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MLKL mediates apoptosis via a mutual regulation with PERK/eIF2 alpha pathway in response to reactive oxygen species generation
Wen‑Xiang Cao; Ting Li; Zheng‑Hai Tang; Le‑Le Zhang; Zhao‑Yu Wang; Xia Guo; Min‑Xia Su; Xiuping Chen; Jin‑Jian Lu
2018-08-06
Source PublicationAPOPTOSIS
ISSN1360-8185
Volume23Issue:9-10Pages:521-531
Abstract

The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a core effector of necroptosis, and its function in necroptosis is widely studied. However, the function of MLKL in apoptosis remains unclear. In the present study, the role of MLKL in chelerythrine (CHE)-promoted apoptosis was studied. A special band of MLKL (i.e., *MLKL) was observed after treatment with CHE. MLKL and *MLKL were accumulated in the nucleus upon treatment with CHE and MLKL silencing reversed the CHE-induced apoptosis. Blockade of CHE-triggered reactive oxygen species (ROS) generation or inhibition of CHE-activated protein kinase-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2 α subunit (eIF2α) pathway reversed the apoptosis. A decreased ROS level inhibited CHE-mediated nuclear translocation of MLKL and *MLKL and the activation of eIF2α, whereas MLKL or eIF2α silencing did not affect the CHE-triggered ROS generation. Furthermore, MLKL silencing prevented the CHE-activated eIF2α signal, and eIF2α silencing blocked the CHE-induced nuclear translocation of MLKL and *MLKL. Our studies suggested that CHE possibly induces apoptosis through the nuclear translocation of MLKL and *MLKL, which is promoted by a mutual regulation between MLKL and PERK–eIF2α pathway in response to ROS formation. The present study clarified the new function of MLKL in apoptosis.

KeywordMlkl Eif2α Ros Apoptosis Chelerythrine
DOI10.1007/s10495-018-1475-6
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000446064700006
PublisherSPRINGER, VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
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Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorJin‑Jian Lu
AffiliationState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 7014, N22, Avenida da Universidade, Taipa, Macao, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wen‑Xiang Cao,Ting Li,Zheng‑Hai Tang,et al. MLKL mediates apoptosis via a mutual regulation with PERK/eIF2 alpha pathway in response to reactive oxygen species generation[J]. APOPTOSIS,2018,23(9-10):521-531.
APA Wen‑Xiang Cao.,Ting Li.,Zheng‑Hai Tang.,Le‑Le Zhang.,Zhao‑Yu Wang.,...&Jin‑Jian Lu.(2018).MLKL mediates apoptosis via a mutual regulation with PERK/eIF2 alpha pathway in response to reactive oxygen species generation.APOPTOSIS,23(9-10),521-531.
MLA Wen‑Xiang Cao,et al."MLKL mediates apoptosis via a mutual regulation with PERK/eIF2 alpha pathway in response to reactive oxygen species generation".APOPTOSIS 23.9-10(2018):521-531.
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