Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells
Joint Authors
Jin, Si
Bai, Xiangli
Jia, Xiong
Lu, Yajing
Zhu, Lin
Zhao, Ying
Cheng, Wenzhuo
Shu, Meng
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-21, 21 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-06-24
Country of Publication
Egypt
No. of Pages
21
Main Subjects
Abstract EN
Subendothelial retention of apolipoprotein B100-containing lipoprotein, such as low-density lipoprotein (LDL), is the initial step of atherogenesis.
Activation of autophagy exhibits beneficial effects for the treatment of atherosclerosis.
In our previous study, we demonstrated that hyperglycemia suppressed autophagic degradation of caveolin-1, which in turn resulted in acceleration of caveolae-mediated LDL transcytosis across endothelial cells and lipid retention.
Therefore, targeting the crossed pathway in autophagy activation and LDL transcytosis interruption may be a promising antiatherosclerotic strategy.
In metabolic diseases, including atherosclerosis, salidroside, a phenylpropanoid glycoside compound (3,5-dimethoxyphenyl) methyl-β-glucopyranoside), is the most important compound responsible for the therapeutic activities of Rhodiola.
However, whether salidroside suppresses LDL transcytosis to alleviate atherosclerosis has not yet been elucidated.
In the present study, we demonstrated that salidroside significantly decreased LDL transcytosis across endothelial cells.
Salidroside-induced effects were dramatically blocked by AMPK (adenosine monophosphate-activated protein kinase) inhibitor (compound c, AMPKα siRNA) and by overexpression of exogenous tyrosine-phosphorylated caveolin-1 using transfected cells with phosphomimicking caveolin-1 on tyrosine 14 mutant plasmids (Y14D).
Furthermore, we observed that salidroside promoted autophagosome formation via activating AMPK.
Meanwhile, the interaction between caveolin-1 and LC3B-II, as well as the interaction between active Src (indicated by the phosphorylation of Src on tyrosine 416) and LC3B-II, was significantly increased, upon stimulation with salidroside.
In addition, both bafilomycin A1 (a lysosome inhibitor) and an AMPK inhibitor (compound c) markedly prevented salidroside-induced autophagic degradation of p-Src and caveolin-1.
Moreover, the phosphorylation of caveolin-1 on tyrosine 14 was disrupted due to the downregulation of p-Src and caveolin-1, thereby directly decreasing LDL transcytosis by attenuating the number of caveolae on the cell membrane and by preventing caveolae-mediated LDL endocytosis released from the cell membrane.
In ApoE-/- mice, salidroside significantly delayed the formation of atherosclerotic lesions.
Meanwhile, a significant increase in LC3B, accompanied by attenuated accumulation of the autophagy substrate SQSTM1, was observed in aortic endothelium of ApoE-/- mice.
Taken together, our findings demonstrated that salidroside protected against atherosclerosis by inhibiting LDL transcytosis through enhancing the autophagic degradation of active Src and caveolin-1.
American Psychological Association (APA)
Bai, Xiangli& Jia, Xiong& Lu, Yajing& Zhu, Lin& Zhao, Ying& Cheng, Wenzhuo…[et al.]. 2020. Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1206099
Modern Language Association (MLA)
Bai, Xiangli…[et al.]. Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-21.
https://search.emarefa.net/detail/BIM-1206099
American Medical Association (AMA)
Bai, Xiangli& Jia, Xiong& Lu, Yajing& Zhu, Lin& Zhao, Ying& Cheng, Wenzhuo…[et al.]. Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1206099
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1206099