The polyphenol quercetin protects from glucotoxicity depending on the aggresome in Caenorhabditis elegans

Civelek, Mehtap; Flory, Sandra; Meloh, Hedda; Fitzenberger, Elena; Wenzel, U.

doi:10.1007/s00394-019-01917-6

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…Aggresome appearance associated with the expression of human neurodegenerative disease proteins [69, 70] or ROS stresses [71] have been reported for C. elegans cells, but the data we present contributes the first multi-component characterization of C. elegans neuronal aggresomes and definitively establishes that aggresome formation mechanisms are conserved from nematodes to humans. C. elegans are thus a legitimate model for deciphering the relative role of aggresomes in maintaining neuronal proteostasis in an in vivo context.…”

Section: Discussionmentioning

confidence: 56%

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Intermediate Filaments Associate with Aggresome-like Structures in ProteostressedC. elegansNeurons and Influence Large Vesicle Extrusions as Exophers

Arnold

Cooper

Androwski

et al. 2022

Preprint

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In human neurodegenerative diseases, toxic protein aggregates can spread between neurons to promote pathology. In the transparent genetic animal model C. elegans, stressed neurons can concentrate fluorescently tagged protein aggregates and organelles and extrude them in large, nearly soma-sized, membrane-bound vesicles called exophers that enter neighboring cells. C. elegans exophergenesis may occur by mechanisms analogous to those that enable aggregate spreading in the human brain in neurodegenerative disease. Here we report on aggresome-like biology in stressed C. elegans neurons that influences exophergenesis. We show that C. elegans intermediate filament proteins IFD-1 and IFD-2 can assemble into juxtanuclear structures with characteristics similar to mammalian aggresomes and document that these intermediate filaments are required cell autonomously for efficient exopher production. IFD-concentrating structures expand with age or neuronal stress level, can associate with neurotoxic polyglutamine expansion protein HttQ74, and depend upon orthologs of mammalian adapter proteins, dynein motors, and microtubule integrity for collection of aggregates into juxtanuclear compartments. IFD homolog human neurofilament light chain hNFL can substitute for C. elegans IFD-2 proteins in promoting exopher production, indicating conservation of the capacity of intermediate filaments to influence neuronal extrusion. In sum, we identify an unexpected requirement for specific intermediate filaments, counterparts of human biomarkers of neuronal injury and disease, and major components of Parkinson’s disease Lewy bodies, in large vesicle extrusion from stressed neurons.

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Section: Discussionmentioning

confidence: 56%

“…Aggresome appearance associated with the expression of human neurodegenerative disease proteins [69,70] or ROS stresses [71] Aggresome-related mechanisms influence exopher levels. Our data implicate aggresomeassociated proteins that collect and associate with protein aggregates in promoting exophergenesis levels.…”

Section: Discussionmentioning

confidence: 99%

Intermediate Filaments Associate with Aggresome-like Structures in ProteostressedC. elegansNeurons and Influence Large Vesicle Extrusions as Exophers

Arnold

Cooper

Androwski

et al. 2022

Preprint

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“…There have been reports of polyphenols reducing fat content in C. elegans by reducing the food intake [ 20 ], increasing lipolysis [ 2 ], inhibiting lipogenesis [ 79 ], and through different pathways [ 7 , 55 , 59 , 77 ]. Regarding the compounds found in our ethanolic extracts, quercetin has proved to protect C. elegans from glucotoxicity [ 14 ], vanillic and ellagic acid reduced fat content in the nematode [ 2 ], and the latter increases its lifespan [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic and anti-obesity properties of a polyphenol-rich flower extract from Tagetes erecta L. and its effects on Caenorhabditis elegans fat storages

et al. 2023

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Diabetes mellitus (DM) is a metabolic disease characterized by a high blood sugar level that can cause severe complications to the organism or even death when not treated. However, certain dietary habits and foods may have beneficial effects on this condition. A polyphenolic-rich extract (containing hyperoside, isoquercitrin, quercetin, ellagic acid, and vanillic acid) of Tageres erecta L. (T. erecta) was obtained from yellow and orange flowers using an ethanolic Soxhlet extraction. These extracts were screened for antidiabetic and anti-obesity properties using in vitro and in vivo procedures. The capacity to inhibit the enzymes lipase and α-glucosidase, as well as the inhibition of advance glycation end-products (AGEs) was tested in vitro. Caenorhabditis elegans (C. elegans) was used as an obesity in vivo model to assess extracts effects on fat accumulation using the wild-type strain N2 and a mutant with no N3 fatty acid desaturase activity BX24. Extracts from both cultivars (yellow and orange) T. erecta presented in vitro inhibitory activity against the enzymes lipase and α-glucosidase, showing lower IC50 values than acarbose (control). They also showed important activity in preventing AGEs formation. The polyphenol-rich matrices reduced the fat content of obese worms in the wild-type strain (N2) down to levels of untreated C. elegans, with no significant differences found between negative control (100% reduction) and both tested samples (p < 0.05). Meanwhile, the fat reduction was considerably lower in the BX24 mutants (fat-1(wa-9)), suggesting that N3 fatty acid desaturase activity could be partially involved in the T. erecta flower effect. Our findings suggested that polyphenols from T. erecta can be considered candidate bioactive compounds in the prevention and improvement of metabolic chronic diseases such as obesity and diabetes.

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“…Plant-based nutrients as mainly recommended in the so-called Mediterranean diet contain numerous phytochemicals mediating wholesome effects. In particular, the major group of polyphenols was reported to wield protective properties, e.g., ameliorating glucotoxicity [205,206], oxidative stress [207], and ER stress [208] as well as inhibiting α-amylase [209,210] and preventing protein glycation [211]. Yet, their effects on the mitochondria of β-cells have been barely investigated (in cell lines: n = 5, in animal experiments: n = 5).…”

Section: Potential Protective Effects Of Plant-based Nutrientsmentioning

confidence: 99%

Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review

2021

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Lipotoxicity is a major contributor to type 2 diabetes mainly promoting mitochondrial dysfunction. Lipotoxic stress is mediated by elevated levels of free fatty acids through various mechanisms and pathways. Impaired peroxisome proliferator-activated receptor (PPAR) signaling, enhanced oxidative stress levels, and uncoupling of the respiratory chain result in ATP deficiency, while β-cell viability can be severely impaired by lipotoxic modulation of PI3K/Akt and mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) pathways. However, fatty acids are physiologically required for an unimpaired β-cell function. Thus, preparation, concentration, and treatment duration determine whether the outcome is beneficial or detrimental when fatty acids are employed in experimental setups. Further, ageing is a crucial contributor to β-cell decay. Cellular senescence is connected to loss of function in β-cells and can further be promoted by lipotoxicity. The potential benefit of nutrients has been broadly investigated, and particularly polyphenols were shown to be protective against both lipotoxicity and cellular senescence, maintaining the physiology of β-cells. Positive effects on blood glucose regulation, mitigation of oxidative stress by radical scavenging properties or regulation of antioxidative enzymes, and modulation of apoptotic factors were reported. This review summarizes the significance of lipotoxicity and cellular senescence for mitochondrial dysfunction in the pancreatic β-cell and outlines potential beneficial effects of plantbased nutrients by the example of polyphenols.

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The polyphenol quercetin protects from glucotoxicity depending on the aggresome in Caenorhabditis elegans

Cited by 5 publications

References 30 publications

Intermediate Filaments Associate with Aggresome-like Structures in ProteostressedC. elegansNeurons and Influence Large Vesicle Extrusions as Exophers

Intermediate Filaments Associate with Aggresome-like Structures in ProteostressedC. elegansNeurons and Influence Large Vesicle Extrusions as Exophers

Antidiabetic and anti-obesity properties of a polyphenol-rich flower extract from Tagetes erecta L. and its effects on Caenorhabditis elegans fat storages

Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review

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