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	Hong-Juan Hu, Ze-Ya Shi, Xiao-Lin Lin, San-Mei Chen, Qing-Yan Wang, Si-Yuan Tang
Journal	DNA and cell biology (DNA Cell Biol) Vol. 34 Issue 4 Pg. 296-302 (Apr 2015) ISSN: 1557-7430 [Electronic] United States
PMID	25692450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Lipoproteins, LDL Nuclear Proteins RNA, Messenger Reactive Oxygen Species SESN2 protein, human oxidized low density lipoprotein JNK Mitogen-Activated Protein Kinases
Topics	Apoptosis Blotting, Western Cell Proliferation Cells, Cultured Flow Cytometry Gene Expression Regulation Humans Immunoenzyme Techniques JNK Mitogen-Activated Protein Kinases (genetics, metabolism) Lipoproteins, LDL (genetics, metabolism) Macrophages (metabolism, pathology) Nuclear Proteins (genetics, metabolism) RNA, Messenger (genetics) Reactive Oxygen Species (metabolism) Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction

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