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Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress.

Sirtuin 1 (Sirt1) exerts its cardioprotective effects in various cardiovascular diseases via multiple cellular activities. However, the therapeutic implications of Sirt1 in hypoxic cardiomyocytes and the underlying mechanisms remain elusive. The present study investigated whether Sirt1 regulates autophagy and apoptosis in hypoxic H9C2 cardiomyocytes and in an experimental hypoxic mouse model. Right ventricular outflow tract biopsies were obtained from patients with cyanotic or acyanotic congenital heart diseases. Adenovirus Ad‑Sirt1 was used to activate Sirt1 and Ad‑Sh‑Sirt1 was used to inhibi…

Redd1 protects against post‑infarction cardiac dysfunction by targeting apoptosis and autophagy.

Post‑infarction remodeling is accompanied and influenced by perturbations in the mammalian target of rapamycin (mTOR) signaling. Regulated i … index. Additionally, Redd1 overexpression resulted in suppressed myocardial apoptosis and improved autophagy. Furthermore, the studies revealed that Redd1 overexpression could inhibit the phosphorylation of mTOR and its downstream effectors P70/S6 kinase and 4EBP1. In conclusion, this study demonstrated that Redd1 overexpression protects against the develo …

Curcumin-activated autophagy plays a negative role in its anti-osteoclastogenic effect.

BACKGROUND/PURPOSE: It remains unclear what role curcumin plays in the autophagy of osteoclast precursors (OCPs) during osteoclastogenesis, since some researchers found that curcumin has the ability to inhibit osteoclastogenesis. While others have considered it as an autophagy activator. This study aimed to determine the effect of curcumin-regulated autophagy on osteoclastogenesis. RESULTS: The results revealed that direct administration of curcumin enhanced the OCP autophagy response in bone marrow-derived macrophages (BMMs). Curcumin could also abate RANKL's stimulatory effect on OCP autoph…

Autophagy protects against retinal cell death in mouse model of cytomegalovirus retinitis.

BACKGROUND: Extensive death of uninfected bystander neuronal cells is an important component of the pathogenesis of cytomegalovirus retinitis (CMV). Our previous results have shown that there is a functional relationship between autophagy and apoptosis during MCMV infection of retinal pigment epithelium (RPE). The purpose of this study was to determine whether autophagy plays a significant role in the death of retinal cells during MCMV retinitis. METHODS: The retinas of adult BALB/c mice were infected with MCMV via supraciliary injection. Rapamycin, a mTOR inhibitor, was injected to MCMV-infe…

MeCP2 препятствует функционированию клеток через FoxO3a и автофагию в клетках эндотелиальных потомков.

ЦЕЛИ: Автофагия представляет собой эволюционный механизм внутриклеточной деградации, в рамках которого клеточные компоненты получают фагоцитоза для поддержания клеточной гомеостазии. Блок O 3a (FoxO3a) пропагандирует автофагию для защиты клеток от экологического стресса. Метилированный CpG связывающий протеин 2 (MeCP2) — ядерный протеин, связывающий ДНК и подавляющий транскрипцию. Однако механизм и взаимодействие между FoxO3a и MeCP2, лежащая в основе эндотелиального потомка (EPC), не в полной мере понимаются. МЕРОПРИЯТИЯ: В ЕРЦ MeCP2 перевыражённая автофагика и функциональность клеток, которы

Совпадение в аннотации оригинала
OBJECTIVES: Autophagy is an evolutionarily conserved intracellular degradation mechanism in which cell constituents are phagocytosed to maintain cellular homeostasis. Forkhead box O 3a (FoxO3a) promotes autophagy to protect cells from environmental stress. Methylated CpG binding protein 2 (MeCP2) is a nuclear protein that binds DNA and represses transcriptio…

[Fructose-1, 6-bisphosphatase inhibits autophagy and proliferation in liver cancer cells].

Objective: To construct the recombinant adenoviral containing fructose 1, 6-biphosphatase 1 (FBP1), and to investigate whether FBP1 has effect on autophagy and proliferation in liver cancer cells (HepG2). Methods: FBP1 cDNA sequence was amplified by PCR and cloned in adenovirus vector pAdTrack-TO4, and then recombinant adenovirus plasmid pAdTrack-FBP1 was constructed. The recombinant adenovirus plasmid was transfected into HEK293 cells by Lipofectamine 3000. High-titer of recombinant adenovirus AdFBP1 was obtained by packaging and amplification. HepG2 cells were infected with recombinant adeno…

Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.

Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both…

Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis.

Macroautophagy/autophagy is considered as an evolutionarily conserved cellular catabolic process. In this study, we aimed to elucidate the role of autophagy in vascular smooth muscle cells (SMCs) on atherosclerosis. SMCs cultured from mice with SMC-specific deletion of the essential autophagy gene atg7 (Atg7cKO) showed reduced serum-induced cell growth, increased cell death, and decreased cell proliferation rate. Furthermore, 7-ketocholestrerol enhanced apoptosis and the expression of CCL2 (chemokine [C-C motif] ligand 2) with the activation of TRP53, the mouse ortholog of human and rat TP53, …

TREM-1 Inhibition Restores Impaired Autophagy Activity and Reduces Colitis in Mice.

BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells-1 [TREM-1] is known to amplify inflammation in several diseases. Autophagy and endoplasmic reticulum [ER] stress, which activate the unfolded protein response [UPR], are closely linked and defects in these pathways contribute to the pathogenesis of inflammatory bowel disease [IBD]. Both autophagy and UPR are deeply involved in host-microbiota interactions for the clearance of intracellular pathogens, thus contributing to dysbiosis. We investigated whether inhibition of TREM-1 would prevent aberrant inflammation by modulating a…

Nicotinamide-N-methyltransferase controls behavior, neurodegeneration and lifespan by regulating neuronal autophagy.

Nicotinamide N-methyl-transferase (NNMT) is an essential contributor to various metabolic and epigenetic processes, including the regulating … hionine. Thereby, it regulates the catalytic capacities of LCMT-1, targeting NPRL-2, a regulator of autophagy. Autophagy is a core cellular, catabolic process for degrading cytoplasmic material, but very little is known about the regulation of autophagy during aging. We report an important role for NNMT in regulation of autophagy during aging, where high ne …

Autophagy Dysfunction and Oxidative Stress, Two Related Mechanisms Implicated in Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is one of the most common clinical subtypes of retinal degeneration (RD), and it is a neurodegenerative disease that could cause complete blindness in humans because it ultimately affects the photoreceptors viability. RP afflicts an estimated 1.5 million patients worldwide. The retina is highly susceptible to oxidative stress which can impair mitochondrial function. Many retina pathologies, such as diabetic retinopathy and secondary cone photoreceptor death in RP, have been related directly or indirectly with mitochondrial dysfunction. The possible role of autophagy i…

Inhibition of autophagy enhances adenosine‑induced apoptosis in human hepatoblastoma HepG2 cells.

In cancer research, autophagy acts as a double‑edged sword: it increases cell viability or induces cell apoptosis depending upon the cell context and functional status. Recent studies have shown that adenosine (Ado) has cytotoxic effects in many tumors. However, the role of autophagy in Ado‑induced apoptosis is still poorly understood. In the present study, Ado‑induced apoptotic death and autophagy in hepatoblastoma HepG2 cells was investigated and the relationship between autophagy and apoptosis was identified. In the present study, it was demonstrated that Ado inhibited HepG2 cell growth in …

Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis.

The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease … ria, which accumulated in untreated Cox15sm/sm mice. Conversely, rilmenidine, an mTORC1-independent autophagy inducer, was ineffective on the myopathic features of Cox15sm/sm animals. This stark difference supports the idea that inhibition of mTORC1 by rapamycin has a key role in the improvement of the mitochondrial function in Cox15sm/sm muscle. In contras …

Salinomycin ameliorates oxidative hepatic damage through AMP-activated protein kinase, facilitating autophagy.

Salinomycin, a monocarboxylic ionophore in Streptomyces albus, has been studied as an anti-cancer agent. However, we wondered whether salino … ptosis, mitochondrial dysfunction and ROS production. As a molecular mechanism, salinomycin induced autophagy through AMP-activated protein kinase (AMPK) activation, as assessed by the accumulation of acidic vesicle organelles, p62 and LC3-II. Moreover, these protective effects were blocked by AMPK inhibition, which indicates the importance of AMPK in the p …

Schwann-Cell Autophagy, Functional Recovery, and Scar Reduction After Peripheral Nerve Repair.

The functional outcome after peripheral nerve repair is often unpredictable for many reasons, e.g., the severity of neuronal death and scarring. Axonal degeneration significantly affects outcomes. Post-injury axonal degeneration in peripheral nerves is accompanied by myelin degradation initiated by Schwann cells (SCs), which activate autophagy, a ubiquitous cytoprotective process essential for degrading and recycling cellular constituents. Scar formation occurs concomitantly with nerve insult and axonal degeneration. The association between SC autophagy and the mechanisms of nerve scar formati…

[Rosuvastatin protects acute myocardial infarction rats through autophagy regulation via AMPK signaling].

Objective: To investigate the effects of rosuvastatin (RSV)on autophagy and apoptosis of myocardial cells in rats with acute myocardial infarction. Methods: SD rats were divided into control (Sham group), acute myocardial infarction model rats (AMI group), AMI rats treated by RSV with the dose of 5 mg·kg(-1)·d(-1) (RSV group), AMI rats treated by RSV and AMPK inhibitor Compound C at the same time (RSV+ CC group)(n=8) based on simple random sampling methods.Rat myocardial cell line H9c2 was divided into control group, Hypoxia group, Hypoxia+ RSV group, Hypoxia+ RSV+ Compound C group, Hypoxia+ A…

AMP-activated protein kinase stimulates osteoblast differentiation and mineralization through autophagy induction.

Previous studies have reported that adenosine monophosphate‑activated protein kinase (AMPK) activation can enhance osteoblast differentiation and mineralization; however, the underlying mechanism is not fully understood. Autophagy also serves an important role in osteoblast mineralization and bone homeostasis. The present study aimed to explore whether activation of AMPK could enhance osteoblast differentiation and mineralization via the induction of autophagy. The fracture healing and nonunion animal models were established and verified by X-ray imaging. Bone maturation was measured by Masson…

TNFAIP3-DEPTOR complex regulates inflammasome secretion through autophagy in ankylosing spondylitis monocytes.

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease with severe inflammatory symptoms in the axial skeleton. The cause … ion. Transmission electron microscopy, the RFP-GFP-LC3 adenovirus, and LC3 expression were used for autophagy detection. Here, we show that TNFAIP3 expression in AS peripheral blood non-classical monocytes was decreased. In normal monocytes, TNFAIP3 induced autophagy, which restricted inflammasome activation to the early stage of LPS stimulation. Zinc-finge …

MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12.

Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is indispensable in maintaining the metabolic activities of cells exposed to deleterious stress. The contribution of microRNA signaling to chondrocyte autophagy in OA development remains elusive. We uncovered an association between poor autophagy and increased miR-128a expressions in articular chondrocytes of patients with end-stage knee OA and in a rat anterior cruciate ligament transection (ACLT) model for OA development. Cartilage matrix degradation and severe OA histopathology was evident upon forced miR-128a express…

Post-translational modifications of Beclin 1 provide multiple strategies for autophagy regulation.

Autophagy is a conserved intracellular degradation pathway essential for protein homeostasis, survival and development. Defects in autophagic pathways have been connected to a variety of human diseases, including cancer and neurodegeneration. In the process of macroautophagy, cytoplasmic cargo is enclosed in a double-membrane structure and fused to the lysosome to allow for digestion and recycling of material. Autophagosome formation is primed by the ULK complex, which enables the downstream production of PI(3)P, a key lipid signalling molecule, on the phagophore membrane. The PI(3)P is genera…