CAV1-CAVIN1-LC3B-mediated autophagy regulates high glucose-stimulated LDL transcytosis

Bai, Xiangli; Yang, Xiaoyan; Xiong, Jun; Rong, Yueguang; Chen, Lulu; Zeng, Tianshu; Deng, Xingming; Li, Wenjing; Wu, Guangjie; Wang, Ling; Li, Ye; Zhang, Jing; Xiong, Zhifan; Xiong, Liang; Wang, Yumei; Zhu, Lin; Zhao, Ying; Jin, Si

doi:10.1080/15548627.2019.1659613

Cited by 56 publications

(46 citation statements)

References 56 publications

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“…Autophagy has been previously implicated in the release of proteins through atypical pathways [50][51][52][53][54] and several studies have linked degradation of CAV1 to autophagy [55][56][57][58][59]. Our EM studies demonstrated abundant small vesicles positive for CAV1 in the cytoplasm of expressing cells.…”

Section: Autophagy Is Critical For the Release Of Cav1 From Lncap Cellssupporting

confidence: 61%

An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells

Ariotti

Okano

et al. 2020

Autophagy

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Section: Autophagy Is Critical For the Release Of Cav1 From Lncap Cellssupporting

confidence: 61%

An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells

Ariotti

Okano

et al. 2020

Autophagy

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“…As illustrated in Figures 3(a) and 3(b) , accumulation of p-Src was decreased by salidroside treatment, which was consistent with a downregulated expression of c-Cbl. In our previous study, we demonstrated that caveolin-1 was recruited to autophagosome for autolysosome degradation by direct interaction with LC3B-II [ 17 ]. Moreover, downregulation of caveolin-1 may lead to a loss in cavin-1 stability [ 37 – 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we demonstrated that caveolin-1 was recruited to the autophagosome for autophagic degradation by directly interacting with LC3B-II [17]. Interestingly, active Src (indicated by autophosphorylation of Src on Tyr 416), which induced the phosphorylation of caveolin-1 on tyrosine 14, was also found to be a target of autophagosome for degradation by their association with autophagy cargo, c-Cbl [36].…”

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confidence: 94%

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Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells

Bai

Xiong

et al. 2020

Oxidative Medicine and Cellular Longevity

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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.

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“…Autophagy has been previously implicated in the release of proteins through atypical pathways [47][48][49][50][51] and several studies have linked degradation of Cav1 to autophagy [52][53][54][55] . Our EM studies demonstrated abundant small vesicles positive for Cav1 in the cytoplasm of expressing cells.…”

Section: Autophagy Is Critical For the Release Of Cav1 From Lncap Cellsmentioning

confidence: 99%

An inverted Caveolin-1 topology defines a novel exosome secreted from prostate cancer cells

Ariotti

Okano

et al. 2020

Preprint

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Caveolin-1 (Cav1) expression and secretion is associated with prostate cancer (PCa) disease progression but the mechanisms underpinning Cav1 release remain poorly understood. Numerous studies have shown Cav1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) Cav1 topology. Here we show that Cav1 can be secreted from specific PCa types in an inverted vesicleassociated form consistent with the features of bioactive Cav1 secretion. Characterization of the isolated vesicles by electron microscopy, single molecule fluorescent microscopy and proteomics reveals they represent a novel class of exosomes ~40 nm in diameter containing ~50-60 copies of Cav1 and strikingly, are released via a non-canonical secretory autophagy pathway. This study provides novel insights into a mechanism whereby Cav1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression.

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CAV1-CAVIN1-LC3B-mediated autophagy regulates high glucose-stimulated LDL transcytosis

Cited by 56 publications

References 56 publications

An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells

An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells

Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells

An inverted Caveolin-1 topology defines a novel exosome secreted from prostate cancer cells

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