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Zika virus infection activates sting-dependent antiviral autophagy in the Drosophila brain.

Viral infection of neurons is pathogenic, yet the factors that govern innate control of neurons remain incompletely understood. Using a Drosophila model we have defined the essential role that inflammatory-dependent Sting activation plays in inducing antiviral macroautophagy/autophagy to restrict Zika infection in the fly brain. Our discovery that Sting is an essential mediator of innate defenses in Drosophila provides further support for an ancient and conserved pathway that likely evolved to target intracellular pathogens for autophagic destruction.

N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy.

Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of…

Classical autophagy proteins LC3B and ATG4B facilitate melanosome movement on cytoskeletal tracks.

Macroautophagy/autophagy is a dynamic and inducible catabolic process that responds to a variety of hormonal and environmental cues. Recent studies highlight the interplay of this central pathway in a variety of pathophysiological diseases. Although defective autophagy is implicated in melanocyte proliferation and pigmentary disorders, the mechanistic relationship between the 2 pathways has not been elucidated. In this study, we show that autophagic proteins LC3B and ATG4B mediate melanosome trafficking on cytoskeletal tracks. While studying melanogenesis, we observed spatial segregation of LC…

Countervailing, time-dependent effects on host autophagy promotes intracellular survival of Leishmania.

Autophagy is essential for cell survival under stress and has also been implicated in host defense. Here, we investigated the interactions between Leishmania donovani, the main etiological agent of visceral leishmaniasis, and the autophagic machinery of human macrophages. Our results revealed that during early infection-and via activation of the Akt pathway-Leishmania actively inhibits the induction of autophagy. However, by 24 h, Leishmania switched from being an inhibitor to an overall inducer of autophagy. These findings of a dynamic, biphasic response were based on the accumulation of lipi…

Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo.

In vitiligo, melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis and to the genetic antioxidant defects. Autophagy is a controlled self-digestion process which can protect cells against oxidative damage. However, the exact role of autophagy in vitiligo melanocytes in response to oxidative stress and the mechanism involved are still not clear. To determine the implications of autophagy for melanocyte survival in response to oxidative stress, we first detected the autophagic flux in normal melanocytes exposure to H2O2, and…

Hydrogen sulfide reduced renal tissue fibrosis by regulating autophagy in diabetic rats.

The present study aimed to explore the effect of hydrogen sulfide (H2S) on renal tissue fibrosis and its mechanism in diabetic rats. Rats we … erine/threonine kinase AKT, transforming growth factor (TGF)‑β1, nuclear factor (NF)‑κB and several autophagy related proteins were assessed by western blot analysis. Compared with the control group, renal tissue fibrosis was observed, collagen IV expression and the 24 h proteinuria quantity was markedly increased and the amount of PAS positive material in …

Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy.

Renal tubular cell apoptosis and tubular dysfunction is an important process underlying diabetic nephropathy (DN). Understanding the mechani … pithelial cells via several complementary assays, including cell viability, cell apoptosis and cell autophagy in the NRK-52E rat kidney tubular epithelial cell line. The extent of apoptosis was significantly increased in the NRK-52E cells following treatment with AGEs. The results also indicated that curcumin reversed this effect by promoting autophagy thro …

Hongjingtian Injection Attenuates Myocardial Oxidative Damage via Promoting Autophagy and Inhibiting Apoptosis.

Natural products with antioxidative activities are widely applied to prevent and treat various oxidative stress related diseases, including … d proteins Bcl-2 and cleaved caspase3. Interestingly, HJT significantly regulated the expression of autophagy-related proteins LC3, Beclin, and mTOR as well as ERK and AKT. We provide evidence that the mechanism involves activation of AKT/Beclin-1, AKT, and ERK/mTOR pathway in cardiomyocyte autophagy. Histological and physiological evaluation revealed that …

FK506 protects heart function via increasing autophagy after myocardial infarction in mice.

OBJECTIVE: To investigate the effect of tacrolimus (FK506) on myocardial infarction, and to further explore its function mechanism. MATERIA … day after MI. Hearts were harvested at 3rd day or 21st day after MI for the detection of apoptosis, autophagy, mTOR and NF-κB pathway. RESULTS: FK506 treatment increased survival rate and cardiac function in mice after MI. It decreased infarction area, inflammation reaction and apoptosis. To further study the mechanism of FK506 protection effect, we discov …

mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy.

The mammalian target of rapamycin complex 1 (mTORC1) kinase promotes cell growth by activating biosynthetic pathways and suppressing catabolic pathways, particularly that of macroautophagy. A prerequisite for mTORC1 activation is its translocation to the lysosomal surface. Deregulation of mTORC1 has been associated with the pathogenesis of several diseases, but its role in skeletal disorders is largely unknown. Here, we show that enhanced mTORC1 signaling arrests bone growth in lysosomal storage disorders (LSDs). We found that lysosomal dysfunction induces a constitutive lysosomal association …

Hydroxytyrosol inhibits the inflammatory response of osteoarthritis chondrocytes via SIRT6-mediated autophagy.

Osteoarthritis (OA) is a common degenerative joint disease. Inflammation may exaggerate the catabolism and degeneration in the pathogenesis of OA. Hydroxytyrosol (HT) has been used in the management of inflammatory diseases. In addition, reports have revealed that autophagy was a therapeutic target of diseases caused by inflammation. Sirtuin 6 (SIRT6) has also been demonstrated to prevent OA development by reducing both the inflammatory response and chondrocyte senescence. However, the roles of SIRT6 and autophagy in cartilage and its underlying anti‑inflammatory mechanism are unknown. Therefo…

Cancer-Associated Fibroblasts Autophagy Enhances Progression of Triple-Negative Breast Cancer Cells.

BACKGROUND Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated. MATERIAL AND METHODS CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts. TNBC cells growth w…

DEV induce autophagy via the endoplasmic reticulum stress related unfolded protein response.

Duck enteritis virus (DEV) can infect ducks, geese, and many other poultry species and leads to acute, septic and highly fatal infectious disease. Autophagy is an evolutionarily ancient pathway that plays an important role in many viral infections. We previously reported that DEV infection induces autophagy for its own benefit, but how this occurs remains unclear. In this study, endoplasmic reticulum (ER) stress was triggered by DEV infection, as demonstrated by the increased expression of the ER stress marker glucose-regulated protein 78 (GRP78) and the dilated morphology of the ER. Pathways …

Зависящая от BECN1 неполная аутопсия CASP2 путем привязки к вирусу бешенства фосфопротеина.

Автофагия является важным компонентом иммунитета хоста и используется вирусами для выживания. Однако автофагические каналы подачи сигналов, связанные с распространением вируса, плохо задокументированы. Здесь мы заметили, что вирус бешенства (RABV) вызывает внутриклеточное аккумулирование автофагосом и приводит к неполной автофагии, подавляя автофагический поток. Впоследствии мы обнаружили, что инфекция RABV привела к сокращению CASP2/caspasa 2 и активации белковой киназы (AMPK)-AKT-MTOR (механистическая цель рэпамицина) и AMPK-MAPK (митогенно активированная белковая киназа). Дальнейшее расслед

Совпадение в аннотации оригинала
Autophagy is an essential component of host immunity and used by viruses for survival. However, the autophagy signaling pathways involved in virus replication are poorly documented. Here, we observed that rabies virus (RABV) infection triggered intracellular autophagosome accumulation and results in incomplete autophagy by inhibiting autophagy flux. Subseque…

Suppression of calcium‑sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy.

The calcium-sensing receptor (CaSR) releases intracellular calcium ([Ca2+]i) by accumulating inositol phosphate. Changes in [Ca2+]i initiate myocardial hypertrophy. Furthermore, autophagy associated with [Ca2+]i. Autophagy has previously been demonstrated to participate in the hypertrophic process. The current study investigated whether suppression of CaSR affects the hypertrophic response via modulating autophagy. Isoproterenol (ISO) was used to induce cardiac hypertrophy in Wistar rats. Hypertrophic status was determined by echocardiographic assessment, hematoxylin and eosin, and Masson's st…

[Valproic acid activates autophagy in multiple myeloma cell lines RPMI8226 and U266].

OBJECTIVE: To investigate the effects of valproic acid (VPA) on autophagy in multiple myeloma (MM) cell lines RPMI8226 and U266. METHODS: The method of dye acridine orange (AO) was used for observing morphological changes of autophagy under fluorescence microscope; The cell proliferation inhibition was measured by MTT assay; Cells apoptosis was evaluated by flow cytometry; Autophagy-related factors LC3, Beclin1 expressions changes were detected by real-time quantitative PCR (Real-time PCR) and western blot assay. RESULTS: AO stainings as dispersively brownish red vesicles were observed both …

Autophagy Promotes Microglia Activation Through Beclin-1-Atg5 Pathway in Intracerebral Hemorrhage.

Previous study demonstrates that intracerebral hemorrhage (ICH) promotes microglia activation and inflammation. However, the exact mechanism of microglia activation induced by ICH is not clear. In this experiment, microglia autophagy was examined using electron microscopy, conversion of light chain 3(LC3), and monodansylcadaverine (MDC) staining to detect autophagic vacuoles. We found that ICH induced microglia autophagy and activation. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (BECN1 an…

Genistein-induced LKB1-AMPK activation inhibits senescence of VSMC through autophagy induction.

Genistein, the primary isoflavone from soy products, enhances antioxidant enzyme activities and inhibits tyrosine kinase. However, the mechanisms underlying genistein-induced autophagy are not yet completely understood. Autophagy refers to a regulated cellular process for the lysosomal-dependent turnover of organelles and proteins. During starvation or nutrient deficiency, autophagy provides an endogenous mechanism for prolonging survival. Here, we investigated whether genistein exerts autophagic effects through the activation of LKB1-AMPK signaling in VSMCs. Genistein dose- and time-dependent…

Vitamin D induces autophagy of pancreatic β-cells and enhances insulin secretion.

Epidemiological evidence indicates that vitamin D is involved in defense against diabetes; however, the precise underlying mechanism remains … on and western blotting were used to determine the mRNA and protein expression levels of markers of autophagy [microtubule-associated protein 1A/1B‑light chain 3 (LC3) and Beclin 1] and regulation of apoptosis [B-cell lymphoma 2 (Bcl-2)]. Apoptosis of MIN6 cells was examined by flow cytometry following annexin V/propidium iodide labeling. The secretion of i …