Результаты поиска

Transcription factor EB (TFEB) promotes autophagy in early brain injury after subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) has high mortality. Early brain injury (EBI) is responsible for unfavorable outcomes for patients with SAH. The protective involvement of autophagy in hemorrhagic stroke has been proposed. The transcription factor EB (TFEB) can increase autophagic flux by promoting autophagosome formation and autophagosome-lysosome fusion, and dysregulation of TFEB activity might induce the development of several diseases. However, the biological functions of TFEB in EBI after SAH remain unknown. We established an animal model of SAH by the modified endovascular perforation method

Inhibition of Autophagy by Berbamine Hydrochloride Mitigates Tumor Immune Escape by Elevating MHC-I in Melanoma Cells.

Impaired tumor cell antigen presentation contributes significantly to immune evasion. This study identifies Berbamine hydrochloride (Ber), a … ing autophagy to enhance MHC-I expression. Additionally, Ber treatment leads to the accumulation of autophagosomes, with elevated levels of LC3-II and p62, suggesting a disrupted autophagic flux. Fluorescence staining and co-localization analyses reveal that Ber likely inhibits lysosomal acidification without hindering autophagosome-lysosome fusion. Importantly, …

Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra.

Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris However, sexual animals from the H. oligactis cold-sensitive strain Ho_CS develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within 3 months. This phenotype is not observed in the cold-resistant strain Ho_CR To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it to be irreversibly reduce

Electroacupuncture Improves Motor Symptoms of Parkinson's Disease and Promotes Neuronal Autophagy Activity in Mouse Brain.

Autophagic defects are a hallmark of neurodegenerative disorders, such as Parkinson's disorder (PD). Enhancing autophagy to remove impaired mitochondria and toxic protein aggregation is an essential component of PD treatment. In particular, activation of autophagy confers neuroprotection in cellular and preclinical models of neurodegenerative diseases. In this study, we investigated the therapeutic mechanisms of electroacupuncture (EA) treatment in mice with established PD and evaluated the relationship between EA, autophagy, and different neurons in the mouse brain. We report that EA improves

Lysosomal Dysfunction and Autophagy Blockade Contribute to MDMA-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

Methylenedioxymethamphetamine (MDMA) is a psychostimulant with high abuse potential and severe neurotoxicity. According to our previous study, MDMA promotes autophagosome accumulation and contributes to cell death in cultured cortical and serotonergic neurons. However, the detailed mechanism underlying autophagy dysfunction remains unclear. Lysosomes play an important role in autophagic degradation. The present study aimed to examine the role of lysosomal function in autophagic flux in neuronal cultures exposed to MDMA. We showed that MDMA induced enlarged vesicles that accumulate in SH-SY5Y n

Hydrogen Sulfide Attenuates β2-Microglobulin-Induced Cognitive Dysfunction: Involving Recovery of Hippocampal Autophagic Flux.

BACKGROUND AND AIM: Accumulation of β2-microglobulin (B2M), a systemic pro-aging factor, regulates negatively cognitive function. Hydrogen sulfide (H2S), a novel gas signaling molecule, exerts protection against cognitive dysfunction. Therefore, the present work was designed to explore whether H2S attenuates cognitive dysfunction induced by B2M and the underlying mechanism. MATERIALS AND METHODS: The cognitive function of rats was assessed by Y-maze, Novel object recognition (NOR), and Morris water maze (MWM) tests. The levels of autophagosome and autolysosome in hippocampus were observed by

Niclosamide Triggers Non-Canonical LC3 Lipidation.

Autophagy is a highly- evolutionarily-conserved catabolic pathway activated by various cellular stresses. Recently, non-canonical autophagy (NCA), which does not require all of the ATG proteins to form autophagosome or autophagosome-like structures, has been found in various conditions. Moreover, mounting evidence has indicated that non-canonical LC3 lipidation (NCLL) may reflect NCA. We and others have reported that niclosamide (Nic), an anti-helminthic drug approved by the Food and Drug Administration, could induce canonical autophagy via a feedback downregulation of mTOR complex 1. In this

Armillaridin induces autophagy-associated cell death in human chronic myelogenous leukemia K562 cells.

Armillaridin (AM) is an aromatic ester compound isolated from Armillaria mellea. Treatment with AM markedly reduced the viability of human chronic myelogenous leukemia K562, chronic erythroleukemia HEL 92.1.7, and acute monoblastic leukemia U937 cells, but not normal human monocytes, in a dose- and time-dependent manner. Treatment of K562 cells with AM caused changes characteristic of autophagy. Only a small amount of AM-treated K562 cells exhibited apoptosis. By contrast, AM treatment resulted in extensive apoptotic features in U937 and HEL 92.1.7 cells without evident autophagy. The autophag

RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy.

Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, and its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive and depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) are important factors for the coordination of cellular vesicle transport systems, and several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs are associated with autophagy. Employing C. elegans and human primary fibroblasts, we show that RAB3GAP1 and RAB3GAP2, which are components of …

Simultaneous activation and late-stage inhibition of autophagy induces autophagy-dependent cell death in leukemia.

BACKGROUND: Resistance to apoptosis is a major challenge in cancer therapy, especially in relapsed or refractory leukemia. Autophagy, a cons … endently of both apoptosis and necroptosis, suggesting a direct result of excessive and unprocessed autophagosomes, consistent with ACD. CONCLUSION: In conclusion, our findings demonstrate that trapping cells in a state of high autophagic flux through simultaneous induction and late stage inhibition, is a potent strategy to trigger non-apoptotic cell death in l …

Clinical and biochemical footprints of inherited disorders of autophagy.

Autophagy is an evolutionarily conserved lysosomal recycling system that integrates nutrient sensing, organelle quality control, proteostasis, cellular stress responses and metabolic adaptation. Autophagy is particularly relevant for post-mitotic tissue such as neurons, skin, and immune cells. Monogenic disorders disrupting autophagy or closely coupled endolysosomal trafficking pathways have recently emerged as a recognizable group of inherited metabolic diseases. These conditions are individually rare inborn errors of metabolism and collectively important because they bridge neurodevelopmenta

Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway.

OBJECTIVES: Neiyi Prescription of QIU (NYPQ) is a traditional Chinese medicine prescription for the treatment of endometriosis (EMS). Here, … he endometriotic lesions was measured. The pathological morphology, angiogenesis, and the number of autophagosomes of the endometriotic lesion were observed by hematoxylin and eosin staining, immunohistochemistry, and transmission electron microscope, respectively. The cell viability, apoptosis, and angiogenesis of HUVECs were detected by MTT, flow cytometry, an …

Isoliquiritigenin inhibits pancreatic cancer progression through blockade of p38 MAPK-regulated autophagy.

BACKGROUND: Pancreatic cancer has been characterized by poor prognosis, early metastasis and dissatisfactory treatment outcome. The high bas … pancreatic cancer cells. Apoptosis were analyzed using TUNEL and flow cytometry. The formations of autophagosomes were analyzed by immunofluorescence microscopy and transmission electron microscopy. RFP-GFP-LC3B probe was applied to detect the autophagy flux. To assess the structural interaction of ISL with p38 protein, molecular docking assays were performed. …

Члены семей ТБК1 и ГАБАРАП подавляют инфекцию Коксакивируса В путем ограничения вирусного производства и поощрения аутофагической деградации вирусных внеклеточных везиков.

Динамия гостиничного патогена постоянно идёт во время инфекции. Coxsackievirus B (CVB) — обычный взрослый энтеровирус, который заражает множество органов и воздействует на подстрекательские заболевания, включая острый панкреатит и миокардит. Как и другие энтеровирусы, CVB способен манипулировать хостинговыми машинами, чтобы угонять и разрушать автофагию. Ранее мы сообщали, что CVB приводит к высвобождению инфекционных внеклеточных везикол (ЭМ), которые возникают от автофагосом. Эти ЭМ способствуют эффективному распространению инфекционных вирусов. Здесь мы сообщаем, что TBK1 (Tank-cynase 1) по

Совпадение в аннотации оригинала
Host-pathogen dynamics are constantly at play during enteroviral infection. Coxsackievirus B (CVB) is a common juvenile enterovirus that inf … orted that CVB triggers the release of infectious extracellular vesicles (EVs) which originate from autophagosomes. These EVs facilitate efficient dissemination of infectious virus. Here, we report that TBK1 (Tank-binding kinase 1) suppresses release of CVB-induced EVs. TBK1 is a multimeric kinase that directly activates autophagy adaptors for efficient cargo re …

The atypical small GTPase GEM/Kir is a negative regulator of the NADPH oxidase and NETs production through macroautophagy.

Despite the important function of neutrophils in the eradication of infections and induction of inflammation, the molecular mechanisms regul … ocytosis of gelatinase and azurophilic granules. Gem-deficiency was associated with increased basal autophagosomes and autolysosome numbers but decreased autophagic flux under phorbol ester-induced conditions. Neutrophil stimulation triggered the localization of the NADPH oxidase subunits p22phox and p47phox at LC3-positive structures suggesting that the assembl …

A novel transgenic zebrafish line allows for in vivo quantification of autophagic activity in neurons.

The pathophysiology of most neurodegenerative diseases includes aberrant accumulation of protein aggregates. Recent evidence highlights the … We determined the applicability of this transgenic line by modulating and quantifying the number of autophagosomes via treatment with a known autophagy inducer (rapamycin) and inhibitors (3-methyladenine, protease inhibitors). Additionally, we proposed an in vivo method for quantifying rates of autophagosome accumulation, which can be used to infer occurrence of …

[Effect of Agkistrodon Acutus Venom PCA on HUVEC Activity].

OBJECTIVE: To investigate the effects of Agkistrodon acutus venom protein C activator(PCA) on ultrastructure of human umbilical vein endothelial cells(HUVEC), and the levels of tissue factor(TF), vascular von Willebrand factor (vWF) and endothelin-1 secreted by HUVEC and to clarify the anti-thrombotic mechanism of PCA. METHODS: The experiments were divided into control group(DMEM), LPS group (LPS 0.1 µg/ml), PCA group(PCA 1 µg/ml) and PCA+LPS group (1 µg/ml PCA+ 0.1 µg/ml LPS). The morphology of endoplasmic reticulum, mitochondria and the number of autophagosome in HUVEC were observed by tran

PI3K/AKT/mTOR-mediated autophagy in the development of autism spectrum disorder.

AIM: To investigate the association between PI3K/AKT/mTOR-mediated autophagy and the pathogenesis of autism spectrum disorder (ASD). METHOD … ition group (both P<0.05). The control group and the mTOTR inhibition group presented the visual of autophagosomes, while VPA group seldom had autophagosomes. By comparison with VPA group, mTOR group had a remarkable green fluorescence in the hippocampal CA1 (P<0.05). Western Blot assay revealved that mTOR inhibition group had a significantly higher LC3 II expre …

Small bites for big problems: stepwise aggregate degradation by autophagy.

Protein aggregates are a pathological hallmark of diverse disorders, including many neurodegenerative diseases, but also cardiometabolic disease and cancer. While the ubiquitin-proteasome system efficiently removes many soluble misfolded proteins, large or persistent assemblies often require the autophagy-lysosome pathway for their degradation. In the present mini-review, we summarize our knowledge of aggrephagy, the selective clearance of protein aggregates by autophagy, and discuss two recent manuscripts that argue that some aggregates must be primed for autophagosomal degradation, through c

The role of E3 ubiquitin ligases in selective types of macroautophagy.

In contrast to the ubiquitin (Ub)-proteasome-system, which only degrades individual proteins, macroautophagy can eliminate protein complexes or aggregates, organelles and even pathogens. Terms such as mitophagy, aggrephagy, lysophagy and xenophagy have been coined based on the targeted substrate. In Ub-dependent selective macroautophagy, cargo selectivity is specified by E3 Ub ligases that append Ub chains that in turn are recognized by selective autophagy receptors (SARs), driving sequestration into autophagosomes. While several Ub-dependent SARs have been identified and characterized, the E3…