title: Upregulation of Sestrin2 expression protects against macrophage apoptosis induced by oxidized low-density lipoprotein.
abstract: Sestrin2 is involved in a different cellular response to stress conditions. However, the function of Sestrin2 in the cardiovascular system remains unknown. In the present study, we tested whether Sestrin2 has a beneficial effect on macrophage cell apoptosis induced by oxidized low-density lipoprotein (oxLDL). We found that oxLDL induces expression of Sestrin2 in RAW264.7 cells in a time-dependent and dose-dependent manner. We also found that knockdown of Sestrin2 using small RNA interference promotes cell apoptosis and reactive oxygen species production induced by oxLDL. In addition, our results show that the c-Jun NH(2)-terminal kinase (JNK)/c-Jun pathway is activated by oxLDL. Inhibiting the activity of the JNK pathway abolishes the increase of Sestrin2 induced by oxLDL. These findings suggest that the inductive effect of Sestrin2 is mediated by the JNK/c-Jun pathway. Our results indicate that the induction of Sestrin2 acts as a compensatory response to oxLDL for survival, implying that stimulating expression of Sestrin2 might be an effective pharmacological target for the treatment of lipid-related cardiovascular diseases.
authors.affiliation: 1 School of Nursing, Central South University , Changsha City, Hunan Province, People's Republic of China .
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Hu
authors.forename: Ze-Ya
authors.initials: ZY
authors.lastname: Shi
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Lin
authors.forename: San-Mei
authors.initials: SM
authors.lastname: Chen
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Wang
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Tang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000084622:Sestrins
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D008077:Lipoproteins, LDL; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C465398:SESN2 protein, human; D000084622:Sestrins; C099252:oxidized low density lipoprotein