کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1928870 | 1050428 | 2013 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: HDL inhibit endoplasmic reticulum stress by stimulating apoE and CETP secretion from lipid-loaded macrophages HDL inhibit endoplasmic reticulum stress by stimulating apoE and CETP secretion from lipid-loaded macrophages](/preview/png/1928870.png)
• oxLDL induce ER stress in human macrophages.
• 9-HODE-CE and 4-HNE activate ER stress (eIF2α and SAPK/JNK) signaling pathway.
• HDL3 inhibit ER stress by stimulating apoE secretion from lipid-loaded macrophages.
• A new mechanism to diminish ER stress by HDL3 action in macrophages is suggested.
The role of HDL in the modulation of endoplasmic reticulum (ER) stress in macrophage-derived foam cells is not completely understood. Therefore, we aimed to investigate whether HDL may inhibit ER stress in correlation with the secretion of apoE and CETP from lipid-loaded macrophages. To this purpose, THP-1 macrophages were loaded with lipids by incubation with human oxidized LDL (oxLDL) and then exposed to human HDL3. ER stress signaling markers, protein kinase/Jun-amino-terminal kinase (SAPK/JNK p54/p46) and eukaryotic initiation factor-2α (eIF2α), as well as the secreted apoE and CETP, were evaluated by immunoblot analysis. Out of the many different bioactive lipids of oxLDL, we tested the effect of 9-hydroxy-octadecadienoic acid (9-HODE) and 4-hydroxynonenal (4-HNE) on ER stress. Tunicamycin was used as positive control for ER stress induction. Results showed that oxLDL, 9-HODE and 4-HNE induce ER stress in human macrophages by activation of eIF-2α and SAPK/JNK (p54/p46) signaling pathways. OxLDL stimulated apoE and CETP secretion, while tunicamycin determined a reduction of the secreted apoE and CETP, both in control and lipid-loaded macrophages. The addition of HDL3 to the culture medium of tunicamycin-treated cells induced: (i) the reduction of ER stress, expressed as decreased levels of eIF-2α and SAPK/JNK, and (ii) a partial recovery of the secreted apoE and CETP levels in lipid-loaded macrophages. These data suggest a new mechanism by which HDL3 diminish ER stress and stimulate cholesterol efflux from lipid-loaded macrophages.
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Journal: Biochemical and Biophysical Research Communications - Volume 434, Issue 1, 26 April 2013, Pages 173–178