Pdcd4 Is Involved in the Formation of Stress Granule in Response to Oxidized Low-Density Lipoprotein or High-Fat Diet

• Published in: PloS one 2016-07, Vol.11 (7), p.e0159568-e0159568
• Main Authors: Bai, Yang, Dong, Zhaojing, Shang, Qianwen, Zhao, Hui, Wang, Liyang, Guo, Chun, Gao, Fei, Zhang, Lining, Wang, Qun
• Format: Article
• Language: English
• Subjects: AKT protein; Analysis; Animal tissues; Animals; Apoptosis; Apoptosis Regulatory Proteins - deficiency; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Binding; Biology; Biology and Life Sciences; Cancer; Cell death; Cell Line; Cells, Cultured; Cytoplasmic Granules - metabolism; Diet, High-Fat; Disease; Ectopic expression; Eukaryotic Initiation Factor-2 - metabolism; Experiments; Fragile X syndrome; Free radicals; Gene expression; Granular materials; High density lipoprotein; High fat diet; Humans; Immunology; Initiation factor eIF-2α; Intellectual disabilities; Kinases; Lipoproteins; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; Liver; Liver - metabolism; Liver - pathology; Low density lipoprotein; Low density lipoproteins; Lymphocytes T; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Knockout; Obesity; Obesity - genetics; Obesity - metabolism; Oxidative stress; Pathogenesis; Phosphorylation; Protein Transport; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Research and Analysis Methods; Ribonucleic acid; Ribonucleoproteins; RNA; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Stress, Physiological; Stresses; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159568

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.