Thioredoxin upregulation delays diabetes-induced photoreceptor cell degeneration via AMPK-mediated autophagy and exosome secretion

Ren, Xiang; Lv, Jinjuan; Wang, Na; Liu, Jiasu; Gao, Chuanzhou; Wu, Xiaoli; Yu, Yang; Teng, Qiufeng; Dong, Wenkang; Kong, Hui; Kong, Li

doi:10.1016/j.diabres.2022.109788

Cited by 11 publications

(16 citation statements)

References 33 publications

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“…Recently, Lee et al found a link of AMPK with sphingolipid metabolism in platelets, because the increase in sphingomyelin level in H 2 O 2 -treated platelets was prevented by AMPK inhibitor compound C [ 48 ]. The AMPK pathway has been also linked to exosome/microvesicle secretion [ 19 , 20 ]. In cultured adipocytes and white adipose tissue, the absence of AMPKa1 increased exosome release, and AMPK activation by metformin reduced adipocyte-mediated exosome release [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…In cultured adipocytes and white adipose tissue, the absence of AMPKa1 increased exosome release, and AMPK activation by metformin reduced adipocyte-mediated exosome release [ 19 ]. However, inhibition of AMPK has been recently shown to reduce exosome secretion induced by thioredoxin in retinal photoreceptor cells [ 20 ]. In the present study, inhibition of AMPK by compound C reversed rottlerin-promoted exosome/microvesicle secretion and reduction of lipid accumulation in endolysosomes.…”

Section: Discussionmentioning

confidence: 99%

“…AMP-activated protein kinase (AMPK) is a ubiquitous energy-sensing enzyme within cells that is critical in maintaining metabolic homeostasis, and it is a central player in glucose and lipid metabolism [ 18 ]. Recent studies have reported a connection between the AMPK pathway and exosome/microvesicle secretion [ 19 , 20 ]. Moreover, rottlerin activates the AMPK pathway in different cell types [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation

et al. 2022

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Exosomes/microvesicles originate from multivesicular bodies that allow the secretion of endolysosome components out of the cell. In the present work, we investigated the effects of rottlerin, a polyphenol, on exosome/microvesicle secretion in a model of intracellular lipid trafficking impairment, and elucidated the mechanism of action. In a model of lipid trafficking impairment in C6 glia cells, rottlerin increased ceramide levels, while decreasing hexosylceramide content. This was accompanied by increased exosome/microvesicle secretion, thereby reducing the concentration of lipids in the endolysosomal compartment. The reduction of hexosylceramide levels by rottlerin was attributed to the increase of β-glucosidase (glucosylceramidase) activity, and the effects of rottlerin were abrogated by β-glucosidase inhibitors such as isofagomine D-tartrate and AMP-deoxynojirimycin. Moreover, treatment with ML-266, a potent activator of the β-glucosidase enzyme, recapitulated the effects of rottlerin on the sphingolipid profile and exosome/microvesicle secretion. Finally, inhibition of AMPK (AMP-activated protein kinase) using compound C prevented both exosome/microvesicle secretion and the elimination of endolysosome lipids, which were promoted by rottlerin. The results showed that the decrease in intracellular lipid deposition induced by rottlerin was mediated by β-glucosidase activation and exosome/microvesicle release via the AMPK pathway. Rottlerin consumption could represent an additional health benefit in lysosomal deposition diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation

et al. 2022

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“…A decrease in the fluorescence intensity of LC3B was observed in the retina after the knockout of TXNIP in STZ-induced diabetic rats, indicating that autophagy was downregulated ( Ao et al, 2021 ). In addition, we observed the overexpression of Trx, which shows the inhibitory activity of TXNIP, ameliorated photoreceptor cell degeneration in DR via AMPK-mediated autophagy, and exosome secretion ( Ren et al, 2022 ).…”

Section: Txnip In Diabetic Retinal Neurodegenerationmentioning

confidence: 99%

Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy

Liu

Dong

et al. 2022

Front. Neurosci.

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Diabetic retinopathy (DR) is a common complication of diabetes mellitus and has been considered a microvascular disease for a long time. However, recent evidence suggests that diabetic retinal neurodegeneration (DRN), which manifests as neuronal apoptosis, a decrease in optic nerve axons, and reactive gliosis, occurs prior to retinal microvascular alterations. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of thioredoxin (Trx), and it acts by inhibiting its reducing capacity, thereby promoting cellular oxidative stress. In addition, it participates in regulating multiple signaling pathways as a member of the α-arrestin family of proteins. Accumulating evidence suggests that TXNIP is upregulated in diabetes and plays a pivotal role in the pathophysiological process of DR. In this review, we summarized the role of TXNIP in DRN, aiming to provide evidence for DR treatment in the future.

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“…The crosstalk of exosomal secretion and autophagy have been revealed that affected on the treatment of DR. Thioredoxin regulated AMPK-mediated autophagy and exosome secretion to improve diabetes-induced photoreceptor cell degeneration, and might be a beneficial therapy to alleviate retinal photoreceptor cell degeneration and provide for new clinical therapeutic targets for DR [ 99 ].…”

Section: Research Progress Of Exosomes and Autophagy In Retinal Diseasesmentioning

confidence: 99%

Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment

Liu

Yin

et al. 2022

Stem Cell Res Ther

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Background Ocular surface and retinal diseases are widespread problems that cannot be ignored in today’s society. However, existing prevention and treatment still have many shortcomings and limitations, and fail to effectively hinder the occurrence and development of them. Main body The purpose of this review is to give a detailed description of the potential mechanism of exosomes and autophagy. The eukaryotic endomembrane system refers to a range of membrane-bound organelles in the cytoplasm that are interconnected structurally and functionally, which regionalize and functionalize the cytoplasm to meet the needs of cells under different conditions. Exosomal biogenesis and autophagy are two important components of this system and are connected by lysosomal pathways. Exosomes are extracellular vesicles that contain multiple signaling molecules produced by multivesicular bodies derived from endosomes. Autophagy includes lysosome-dependent degradation and recycling pathways of cells or organelles. Recent studies have revealed that there is a common molecular mechanism between exosomes and autophagy, which have been, respectively, confirmed to involve in ocular surface and retinal diseases. Conclusion The relationship between exosomes and autophagy and is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.

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Thioredoxin upregulation delays diabetes-induced photoreceptor cell degeneration via AMPK-mediated autophagy and exosome secretion

Cited by 11 publications

References 33 publications

Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation

Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation

Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy

Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment

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