title: Pdcd4 Is Involved in the Formation of Stress Granule in Response to Oxidized Low-Density Lipoprotein or High-Fat Diet.
abstract: Stress granules (SGs) in response to various stresses have been reported in many diseases. We previously reported the implication of programmed cell death 4 (Pdcd4) in obesity-induced stress responses, but the possible link between Pdcd4 and SGs remains lacking. In this study we showed that oxidized low-density lipoprotein (ox-LDL) or high-fat diet (HFD) induced SG formation in mouse macrophages and liver tissues, and Pdcd4 deficiency in mice remarkably reduced its formation. In response to ox-LDL, either endogenous or ectopic Pdcd4 displayed granule-like expression and co-localized with SG markers including T-cell-restricted intracellular antigen-1, fragile X mental retardation-related protein 1, and eukaryotic initiation factor 4A. Ectopic expression of truncated Pdcd4 that depleted specific RNA-binding motif significantly disrupted the SG formation, suggesting the direct involvement of Pdcd4 in ox-LDL-induced SGs through its RNA-binding activity. Additionally, Pdcd4 deficiency drove AKT activation and suppression of eIF2α phosphorylation, thereby contributing to the resistance to ox-LDL or HFD-induced SG formation. Collectively, our data suggest that Pdcd4 as a crucial regulator in SGs induced by ox-LDL or HFD maybe a potential target for mitigating SG-associated stress responses in obesity and related diseases.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Shang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan 250012, Shandong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, Shandong, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism*; D059305:Diet, High-Fat; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D051017:Apoptosis Regulatory Proteins; D015852:Eukaryotic Initiation Factor-2; D008077:Lipoproteins, LDL; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; C099252:oxidized low density lipoprotein; D051057:Proto-Oncogene Proteins c-akt