title: Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage.
abstract: Our study first proposed that curcumin could protect human endothelial cells from the damage caused by oxidative stress via autophagy. Furthermore, our results revealed that curcumin causes some novel cellular mechanisms that promote autophagy as a protective effect. Pretreatment with curcumin remarkably improves the survival of human umbilical vein endothelial cells (HUVECs) from H 2O 2-induced viability loss, which specifically evokes an autophagic response. Exposed to H 2O 2, curcumin-treated HUVECs upregulate the level of microtubule-associated protein 1 light chain 3-II (LC3-II), the number of autophagosomes, and the degradation of p62. We show that this compound promotes BECN1 expression and inhibits the phosphatidylinositol 3-kinase (PtdIns3K)-AKT-mechanistic target of rapamycin (MTOR) signaling pathway. Curcumin can also reverse FOXO1 (a mediator of autophagy) nuclear localization along with causing an elevated level of cytoplasmic acetylation of FOXO1 and the interaction of acetylated FOXO1 and ATG7, under the circumstance of oxidative stress. Additionally, knockdown of FOXO1 by shRNA inhibits not only the protective effects that curcumin induced, but the autophagic process, from the quantity of LC3-II to the expression of RAB7. These results suggest that curcumin induces autophagy, indicating that curcumin has the potential for use as an autophagic-related antioxidant for prevention and treatment of oxidative stress. These data uncover a brand new protective mechanism involving FOXO1 as having a critical role in regulating autophagy in HUVECs, and suggest a novel role for curcumin in inducing a beneficial form of autophagy in HUVECs, which may be a potential multitargeted therapeutic avenue for the treatment of oxidative stress-related cardiovascular diseases.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, and Department of Pharmacology. School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Xue-Yang
authors.initials: XY
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Lu
authors.initials: L
authors.lastname: Tie
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D003474:Curcumin; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006861:Hydrogen Peroxide; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D020011:Protective Agents; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D058570:TOR Serine-Threonine Kinases; D044764:Ubiquitin-Activating Enzymes; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C491997:BECN1 protein, human; C085126:FOXO1 protein, human; C000716463:rab7 GTP-binding proteins, human; C509349:ATG7 protein, human