endoplasmic reticulum and autophagy

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N , N -dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga)...

Dominant variants in WFS1 (wolframin ER transmembrane glycoprotein), the gene coding for a mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) resident protein, have been associated with Wolfram-like syndrome (WLS). In vitro and in vivo , WFS1 loss results in reduced ER to mitochondria calcium (Ca2+ ) transfer, mitochondrial dysfunction, and enhanced macroautophagy/autophagy and mitophagy. However, in the WLS pathological context, whether the mutant protein triggers the same cellular processes is unknown...

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects...

Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Importin7 (IPO7) is responsible for nucleoplasmic transport of RNAs and proteins, and it has been confirmed to be involved in the development of human cancers. This study aimed to explore the function and mechanism of IPO7 in OSCC. IPO7 expression in tissues and cells was determined by RT-qPCR. Cell proliferative, migratory, and invasive capabilities were detected through transwell assay and colony formation assay. Mice xenograft models were established for evaluating tumor growth...

Autophagy supervises the proteostasis and survival of B lymphocytic cells. Trk-fused gene (TFG) promotes autophagosome-lysosome flux in murine CH12 B cells, as well as their survival. Hence, quantitative proteomics of CH12 tfg KO and WT B cells in combination with lysosomal inhibition should identify proteins that are prone to lysosomal degradation and contribute to autophagy and B cell survival. Lysosome inhibition via NH4 Cl unexpectedly reduced a number of proteins but increased a large cluster of translational, ribosomal, and mitochondrial proteins, independent of TFG...

Perfluoroalkyl sulfonate (PFOS) is a commonly used chemical compound that often found in materials such as waterproofing agents, food packaging, and fire retardants. Known for its stability and persistence in the environment, PFOS can enter the human body through various pathways, including water and the food chain, raising concerns about its potential harm to human health. Previous studies have suggested a cardiac toxicity of PFOS, but the specific cellular mechanisms remained unclear. Here, by using AC16 cardiomyocyte as a model to investigate the molecular mechanisms potential the cardiac toxicity of PFOS...

The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification of Reticulon 4 (Rtn4). Sde proteins have two additional activities of unclear relevance to the infection process: K63 linkage-specific deubiquitination and phosphoribosyl modification of polyubiquitin (pR-Ub). We show here that the deubiquitination activity (DUB) stimulates ER rearrangements while pR-Ub protects the replication vacuole from cytosolic surveillance by autophagy...

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells...

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia...

BACKGROUND: p66Shc, as a redox enzyme, regulates reactive oxygen species (ROS) production in mitochondria and autophagy. However, the mechanisms by which p66Shc affects autophagosome formation are not fully understood. METHODS: p66Shc expression and its location in the trophoblast cells were detected in vivo and in vitro. Small hairpin RNAs or CRISPR/Cas9, RNA sequencing, and confocal laser scanning microscope were used to clarify p66Shc's role in regulating autophagic flux and STING activation...

Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g., p.N370S) and severe (e.g., p.L444P and p.D409H) GBA1 mutations have different PD phenotypes, with differences in age at disease onset, progression, and the severity of motor and non-motor symptoms. We hypothesize that GBA1 mutations cause the accumulation of α-synuclein by affecting the cross-talk between cellular protein degradation mechanisms, leading to neurodegeneration...

Stasimon/Tmem41b is a transmembrane protein with phospholipid scrambling activity that resides in the endoplasmic reticulum and has been implicated in autophagy, lipid metabolism, and viral replication. Stasimon/Tmem41b has also been linked to the function of sensory-motor circuits and the pathogenesis of spinal muscular atrophy. However, the early embryonic lethality of constitutive knockout in mice has hindered the analysis of spatial and temporal requirements of Stasimon/Tmem41b in vivo. To address this, we developed a novel mouse line harboring a conditional knockout allele of the Stasimon/Tmem41b gene in which exon 4 has been flanked by loxP sites (Stas/Tmem41bCKO )...

OBJECTIVE: To study the effects of cadmium on autophagy in germ cells (GC-2 spd cells) through Ca2+ and IRE1 pathway. METHODS: The viability of GC-2 spd cells was determined using a CCK-8 assay to establish the concentration of cadmium treating . MDC staining was employed to assess autophagosome formation. Laser confocal microscopy and flow cytometry were utilized to measure cytoplasmic and endoplasmic reticulum (ER) Ca2+ levels. Western blot was conducted to evaluate the expression levels of proteins associated with the IRE1 signaling pathway and autophagy...

Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements...

Despite the air quality has been generally improved in recent years, ambient fine particulate matter (PM2.5), a major contributor to air pollution, remains one of the major threats to public health. Vascular calcification is a systematic pathology associated with an increased risk of cardiovascular disease. Although the epidemiological evidence has uncovered the association between PM2.5 exposure and vascular calcification, little is known about the underlying mechanisms. The adverse outcome pathway (AOP) concept offers a comprehensive interpretation of all of the findings obtained by toxicological and epidemiological studies...

Heme oxygenase HO-1 (HMOX) regulates cellular inflammation and apoptosis, but its role in regulation of autophagy in Mycoplasma bovis infection is unknown. The objective was to determine how the HO-1/CO- Protein kinase RNA-like endoplasmic reticulum kinase (PERK)-Ca2+ - transcription factor EB (TFEB) signaling axis induces autophagy and regulates clearance of M. bovis by bovine mammary epithelial cells (bMECs). M. bovis inhibited autophagy and lysosomal biogenesis in bMECs and suppressed HO-1 protein and expression of related proteins, namely nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (keap1)...

OBJECTIVES: This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA). MATERIALS AND METHODS: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days...

Dihydromyricetin (DHM) is a natural flavonoid compound with multiple antitumour effects, including inhibition of proliferation, promotion of apoptosis, inhibition of invasion and migration, clearance of reactive oxygen species (ROS) and induction of autophagy. For example, DHM can effectively block the progression of the tumour cell cycle and inhibit cell proliferation. In different types of cancer cells, DHM can regulate the PI3K/Akt pathway, mTOR, and NF-κB pathway components, such as p53, and endoplasmic reticulum stress can alter the accumulation of ROS or induce autophagy to promote the apoptosis of tumour cells...

Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1...

This work was designed to investigate the neurotoxic effects of the typical plasticizer dibutyl phthalate (DBP) using zebrafish larvae as a model. The results of exhibited that zebrafish larvae exposed to DBP at concentrations of 5 μg/L and 10 μg/L exhibited brain malformations (24 h) and behavioral abnormalities (72 h). After 72 hours of exposure to DBP, microglia in the brain were over-activated, reactive oxygen species (ROS) formation was increased, and apoptosis was observed. Meanwhile, it was found that neurons exhibited impaired mitochondrial structure, absent mitochondrial membrane potential and up-regulated autophagy...