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Автофагичные протеины в вирусном экзоцитозе и антивиральных иммунных ответах.

Резюме: Генные закодированные белки, связанные с автоматизацией (Atg), были изначально описаны как имеющие решающее значение для макроаутофаги, катаболического пути разложения цитоплазмических составляющих в лизосомах. Недавно стало ясно, что модули этого механизма могут также использоваться для воздействия на эндо- и экзоцитоз. В этом мини-обзоре обсуждается вопрос о том, как эти альтернативные функции Atg поддерживают воспроизведение вируса и представление вирусного антигена на основных молекулах класса I и II, обладающих гистосопоставимостью (MHC). Более глубокое понимание модульного исполь

Совпадение в аннотации оригинала
Abstract: Autophagy-related (Atg) gene-encoded proteins were originally described for their crucial role in macroautophagy, a catabolic pathway for cytoplasmic constituent degradation in lysosomes. Recently it has become clear that modules of this machinery can also be used to influence endo- and exocytosis. This mini review discusses how these alternative A…

ELMO1 Regulates Autophagy Induction and Bacterial Clearance During Enteric Infection.

Macrophages are specialized phagocytic cells involved in clearing invading pathogens. Previously we reported that engulfment and cell motility protein 1 (ELMO1) in macrophages mediates bacterial internalization and intestinal inflammation. Here we studied the role of ELMO1 in the fate of internalized targets. ELMO1 is present in the intracellular vesicles and enhances accumulation of the protein LC3B following engulfment of Salmonella or treatment with autophagy-inducing rapamycin. The protein ATG5 and the kinase ULK1 are involved in classical autophagy, while LC3-associated phagocytosis is UL…

Potential protective effects of autophagy activated in MPP+ treated astrocytes.

Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and ox…

Targeting non-canonical autophagy overcomes erlotinib resistance in tongue cancer.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) frequently occurs in many human cancers and hampers their therapeutic use. A large body of evidence has demonstrated the pro-survival role of autophagy in many human cancers. However, whether autophagy is involved in the induction of erlotinib resistance in tongue squamous cell carcinoma (TSCC) remains unknown. In this report, we found that autophagy prior to or induced by erlotinib treatment plays an important role in erlotinib resistance in tongue cancer cells. Using LC3 transfection, we observed tha…

Ouabain induces apoptosis and autophagy in Burkitt's lymphoma Raji cells.

The steroid Na+/K+-ATPase blocker ouabain has been shown to exhibit cytotoxic effects in various tumor cell systems. This study aimed to det … microscope (TEM) images of ouabain-treated Raji cells, indicating that these cells were undergoing autophagy. Expression of the autophagy-related proteins LC3-II and Beclin-1 was upregulated in ouabain-treated Raji cells. These results suggest that ouabain may promote cell death in Raji cells by inducing pathways associated with apoptosis and autophagy. Ou …

CD133+ liver cancer stem cells resist interferon-gamma-induced autophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide, and CD133 is a popular cancer stem cell (CSC) ma … 3+ cells increased after IFN-γ treatment of low CD133(+) cell lines. Furthermore, IFN-γ induced the autophagy of low CD133(+) cell lines to decrease proliferation. CONCLUSION: CD133(+) HCC CSCs resisted IFN-γ-induced autophagy, which might also be a mechanism through which CSCs resist immune eradication.

Targeting Notch Signaling and Autophagy Increases Cytotoxicity in Glioblastoma Neurospheres.

Glioblastomas are highly aggressive tumors that contain treatment resistant stem-like cells. Therapies targeting developmental pathways such as Notch eliminate many neoplastic glioma cells, including those with stem cell features, but their efficacy can be limited by various mechanisms. One potential avenue for chemotherapeutic resistance is the induction of autophagy, but little is known how it might modulate the response to Notch inhibitors. We used the γ-secretase inhibitor MRK003 to block Notch pathway activity in glioblastoma neurospheres and assessed its effects on autophagy. A dramatic,…

Autophagy Inhibition Delays Early but Not Late-Stage Metastatic Disease.

The autophagy pathway has been recognized as a mechanism of survival and therapy resistance in cancer, yet the extent of autophagy's function in metastatic progression is still unclear. Therefore, we used murine models of metastatic cancer to investigate the effect of autophagy modulation on metastasis development. Pharmacologic and genetic autophagy inhibition were able to impede cell proliferation in culture, but did not impact the development of experimentally induced 4T1 and B16-F10 metastases. Similarly, autophagy inhibition by adjuvant chloroquine (CQ) treatment did not delay metastasis …

GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy.

Recent progress in chemotherapy has significantly increased its efficacy, yet the development of chemoresistance remains a major drawback. In this study, we show that GFRA1/GFRα1 (GDNF family receptor α 1), contributes to cisplatin-induced chemoresistance by regulating autophagy in osteosarcoma. We demonstrate that cisplatin treatment induced GFRA1 expression in human osteosarcoma cells. Induction of GFRA1 expression reduced cisplatin-induced apoptotic cell death and it significantly increased osteosarcoma cell survival via autophagy. GFRA1 regulates AMPK-dependent autophagy by promoting SRC p…

Autophagy Attenuates MnCl2-induced Apoptosis in Human Bronchial Epithelial Cells.

OBJECTIVE: To investigate the role of autophagy in MnCl2-induced apoptosis in human bronchial epithelial 16HBE cells. METHODS: Cell proliferation was measured by MTT assay. Mitochondrial membrane potential (MMP) and apoptosis were measured by flow cytometry. Autophagic vacuoles were detected by fluorescence microscopy. Cellular levels of apoptosis and autophagy-related proteins were measured by western blotting. RESULTS: 16HBE cell proliferation was inhibited by MnCl2 in a dose- and time-dependent manner. MnCl2-induced 16HBE cell growth inhibition was related to MMP depolarization prior to t…

Silvestrol induces early autophagy and apoptosis in human melanoma cells.

BACKGROUND: Silvestrol is a cyclopenta[b]benzofuran that was isolated from the fruits and twigs of Aglaia foveolata, a plant indigenous to Borneo in Southeast Asia. The purpose of the current study was to determine if inhibition of protein synthesis caused by silvestrol triggers autophagy and apoptosis in cultured human cancer cells derived from solid tumors. METHODS: In vitro cell viability, flow cytometry, fluorescence microscopy, qPCR and immunoblot was used to study the mechanism of action of silvestrol in MDA-MB-435 melanoma cells. RESULTS: By 24 h, a decrease in cyclin B and cyclin D e…

FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes.

Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid droplet (LD) growth in adipocytes. Adipocyte differentiation was associated with upregulation of autophagy and fat specific protein 27 (FSP27), a key regulator of adipocyte maturation and expansion by promoting LD formation and growth. However, FoxO1 …

Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy.

Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes. Canonical autophagy requires all autophagy proteins (ATGs), whereas noncanonical autophagy is activated by diverse agents in which some of the essential autophagy proteins are dispensable. How noncanonical autophagy is induced and/or inhibited is still largely unclear. In this study, we demonstrated that AMDE-1, a recently identified chemical that can induce canonical autophagy, was able to elicit noncanonical autophagy that is independent of the ULK1 (unc-5…

Autophagy protects against cholesterol-induced apoptosis in pancreatic β-cells.

Autophagy is believed to play an important role in maintaining homeostasis in pancreatic β-cells during insulin resistance. This study investigated the role of autophagy in β-cell damage induced by cholesterol and its possible activation mechanism. Rat and mouse pancreatic β-cell lines INS-1 and βTC-6 were incubated with cholesterol alone or in combination with autophagy inhibitors E-64d/Pepstatin A or bafilomycin A1. DAPI staining, western blotting, transmission electron microscopy and immunofluorescence were conducted to assess the effects of autophagy inhibitors on cholesterol-induced apopt…

SIRT6 suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

Reduction in autophagy has been reported to contribute to the pathogenesis of cardiac hypertrophy. However, the molecular pathways leading to impaired autophagy at the presence of hypertrophic stimuli remain to be elucidated. The present study aimed to investigate the role of sirtuin 6 (SIRT6), a sirtuin family member, in regulating cardiomyocyte autophagy, and its implication in prevention of cardiac hypertrophy. Primary neonatal rat cardiomyocytes (NRCMs) or Sprague-Dawley (SD) rats were submitted to isoproterenol (ISO) treatment, and then the hypertrophic responses and changes in autophagy …

PDCD5 protects against cardiac remodeling by regulating autophagy and apoptosis.

Cardiac remodeling, including cardiac hypertrophy and fibrosis, is an important pathological process that can lead to heart failure. A previous study demonstrated that autophagy could represent an active adaptive response in cardiomyocytes that affords protection from cardiac remodeling. In the present study, we investigated the role of an autophagy-related gene, PDCD5 (Programmed cell death 5), in cardiac remodeling induced by β-adrenergic stimulation in vivo. We report for the first time that mice systemically overexpressing PDCD5 (PDCD5tg) were protected from cardiac remodeling. In addition…

First trimester human placental factors induce breast cancer cell autophagy.

Placental factors, progesterone included, facilitate breast cancer cell line (BCCL) motility and thus may contribute to the advanced breast cancer found during pregnancy. Cancer and placental implantations are similar; the last is accompanied by extravillous trophoblast cell invasion and autophagy which are interlinked. We aimed to analyze the effect of first trimester human placenta on BCCL autophagy. BCCLs (MCF-7/T47D) were cultured with placental explants (60 h) or placental supernatants (24 h). Following cultures, BCCLs were sorted out for RNA/protein extraction. RNA served for microarray/…

Mevalonate Pathway Blockade, Mitochondrial Dysfunction and Autophagy: A Possible Link.

The mevalonate pathway, crucial for cholesterol synthesis, plays a key role in multiple cellular processes. Deregulation of this pathway is … osol. Furthermore a severe reduction of protein prenylation has also been associated with defective autophagy, possibly causing inflammasome activation and subsequent cell death. So, it is tempting to hypothesize a mechanism in which defective autophagy fails to remove damaged mitochondria, resulting in increased cell death. This mechanism could play a sign …

Autophagy modulates articular cartilage vesicle formation in primary articular chondrocytes.

Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly characterized; although in some cell types, the generation of extracellular vesicles is associated with up-regulation of autophagy. We sought to determine the role of autophagy in ACV production by primary articular chondrocytes. Using an innovative dynamic model with a light scatter nanoparticle counting apparatus, we determined the effects o…