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Carvacrol protects against λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity by modulating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy.

λ-Cyhalothrin, a type II synthetic pyrethroid, has been widely used in households, agriculture, public health, and gardening to control inse … se parameters approached those of the control group. Increased inflammation, apoptosis, endoplasmic reticulum stress, and autophagy with λ-Cyhalothrin administration reduced with carvacrol co-administration, and liver and kidney tissues were protected from damage, depending on the degree of oxidative stress. After considering all of these data, it was disco …

Mitochondria-associated endoplasmic reticulum membranes dysfunction contributes to PARP-1-dependent cell death under oxidative stress in retinal precursor cells.

Persistent poly (ADP-ribose) polymerase 1 (PARP-1) activation has proven detrimental and can lead to PARP-1-dependent cell death. Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) serve as essential hubs for many biological pathways, such as autophagy and mitochondria fission and fusion. This study aimed to alleviate the effects of hydrogen peroxide (H2 O2 )-induced persistent PARP-1 activation and MAM dysregulation by the usage of a PARP-1 inhibitor. Results showed that receptor-interacting protein kinase (RIPK) 1 inhibitor (necrostatin-1) and PARP-1 inhibitor (olaparib) pro…

Downregulation of ATF-4 Attenuates the Endoplasmic Reticulum Stress-Mediated Neuroinflammation and Cognitive Impairment in Experimentally Induced Alzheimer's Disease Model.

Protein aggregation is invariably associated with the inflammation as a factor in Alzheimer's disease (AD). We investigated the interaction between downstream factors of endoplasmic reticulum (ER) stress pathway and inflammation, with implications in cognitive impairment in AD. Amyloid-β (Aβ)(1-42) was administered by bilateral intracerebroventricular (icv) injection in the brain of adult male Wistar rats to experimentally develop AD. The cognitive impairment was assessed by measuring behavioral parameters such as Morris water maze and novel object recognition tests. Levels of pro-inflammatory…

Nifuroxazide induces the apoptosis of human non‑small cell lung cancer cells through the endoplasmic reticulum stress PERK signaling pathway.

The aim of the present study was to investigate the molecular mechanism of nifuroxazide (NFZ) in the induction of apoptosis of NCI-H1299 human non-small cell lung cancer (NSCLC) cells through the reactive oxygen species (ROS)/Ca2+/protein kinase R-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-DNA damage inducible transcript 3 (CHOP) signaling pathway. Morphological changes of cells were observed by microscopy, and the apoptosis and intracellular ROS levels of cells were observed by inverted fluorescence microscopy. Cell viability after the addition of the PERK inhibitor, GSK26

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… The road of solid tumor survival: From drug-induced endoplasmic reticulum stress to drug resistance. Front Mol Biosci. 2021;8:620514. doi: 10.3389/fmolb.2021.620514. 18. da Costa MOL, Pavani TFA, Lima AN, Scott AL, Ramos DFV, Lazarini M, Rando DGG. … Emerging roles of the endoplasmic reticulum associated unfolded protein response in cancer cell migration and invasion. Cancers (Basel) 2019;11:631. doi: 10.3390/cancers11050631. 31. Oakes SA. Endoplasmic reticulum stress signaling in cancer cells. …

Ochratoxin A triggers endoplasmic reticulum stress through PERK/NRF2 signaling and DNA damage during early embryonic developmental competence in pigs.

Ochratoxin A (OTA), a mycotoxin found in foods, has a deleterious effect on female reproduction owing to its endocrine-disrupting activity mediated through endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the mechanisms of OTA-induced ER stress in pig embryos during in vitro culture (IVC) are not yet fully understood. In the present study, porcine embryos were cultured for two days in an IVC medium supplemented with 0.5, 1.0, and 5.0 μM OTA, which led to an OTA-induced reduction in the developmental rate of blastocysts. The mRNA-seq transcriptome analysi…

Inhibition of TLR4/NF-κB pathway and endoplasmic reticulum stress by overexpressed S100A4 ameliorates retinal ischemia-reperfusion injury of mice.

Retinal ischemia exists in various ischemic retinopathies including glaucoma, contributing to the death of retinal neurons. Calcium binding protein S100A4 is important in tumors, and our previous study found that S100A4 protects retinal ganglion cells (RGCs) against retinal ischemia-reperfusion (I/R) injury. This study was aimed to further discuss the neuroprotection and mechanisms of S100A4 in retinal I/R of mice. The rAAV-EF1α-s100a4-EGFP-WPRE or rAAV-EF1α-EGFP-WPRE-Pa was injected intravitreally 4 weeks before I/R. S100A4, molecules in TLR4 signaling pathway and endoplasmic reticulum (ER) s…

Melatonin Supplementation during In Vitro Maturation of Porcine Oocytes Alleviates Oxidative Stress and Endoplasmic Reticulum Stress Induced by Imidacloprid Exposure.

Imidacloprid (IMI) is an endogenous neonicotinoid insecticide widely used in agriculture and has attracted researchers' attention because of … liorated its toxic effects. Specifically, IMI exposure increased oxidative stress (OS), endoplasmic reticulum stress (ERS), and apoptosis, which may affect polar body expulsion rates and blastocyst formation. Also, IMI exposure reduced oocyte cleavage rates and the number of cells in blastocysts. However, all of these toxic effects can be restored after a m …

Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and induce lipid droplet formation to restrict dengue virus replication.

Wolbachia are a genus of insect endosymbiotic bacteria which includes strains wMel and wAlbB that are being utilized as a biocontrol tool to … ral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, while wPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume in wMel- and wAlbB-infected cell lines and mosquito tissues compared to cells infected with wPip or Wolbachia-fre …

Hsa_circ_0056686, derived from cancer-associated fibroblasts, promotes cell proliferation and suppresses apoptosis in uterine leiomyoma through inhibiting endoplasmic reticulum stress.

Abnormal expression of circular RNAs (circRNAs) in cancer-associated fibroblasts (CAFs) is involved in the tumor-promoting ability of CAFs. … oliferation, migration and apoptosis of ULM cells. CAFs-CM suppressed the expression of endoplasmic reticulum stress (ERS) marker proteins and induced the expression of extracellular matrix (ECM) marker proteins, thus suppressing ERS and increasing ECM accumulation, which could be declined by CAFssh-circ_0056686-CM. Meanwhile, knockdown of hsa_circ_0056686 …

Sarco(endo)plasmic reticulum Ca2+-ATPase function is impaired in skeletal and cardiac muscles from young DBA/2J mdx mice.

The DBA/2J (D2) mdx mouse is a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice. Both D2 and C57 mdx mice exhibited signs of impaired Ca2+ uptake in the gastrocnemius, diaphragm, and left ventricle; however, the level of impairment was more severe in D2 mdx mice. Reductions in maximal SERCA activity were also more prominent in the D2 mdx gastrocnemius and diaphragm when compared to those from C57 …

Transient Receptor Potential Vanilloid Type 1 Protects Against Pressure Overload-Induced Cardiac Hypertrophy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes.

Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel that mediates the relationship between mitochondrial … iomyocyte area and improves mitochondrial function by promoting mitochondria-associated endoplasmic reticulum membranes (MAMs) formation in a phenylephrine-treated cardiomyocyte hypertrophy model. TRPV1 up-regulates the phosphorylation levels of AMP-activated protein kinase and expression of mitofusin2 (MFN2). TRPV1 function is blocked by single-stranded RN …

Protein disulfide isomerases (PDIs) negatively regulate ebolavirus structural glycoprotein expression in the endoplasmic reticulum (ER) via the autophagy-lysosomal pathway.

Zaire ebolavirus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates with high morbidity and mortality. EBOV infection … PDIs promote oxidative protein folding by catalyzing correct disulfide formation in the endoplasmic reticulum (ER), PDIA3/ERp57 adversely triggered the GP misfolding by targeting GP cysteine residues and activated the unfolded protein response (UPR). Abnormally folded GP was targeted by ER-associated protein degradation (ERAD) machinery and, unexpectedly, w …

Porcine epidemic diarrhea virus infection induces endoplasmic reticulum stress and unfolded protein response in jejunal epithelial cells of weaned pigs.

Porcine epidemic diarrhea virus (PEDV) infection leads to diarrhea and subsequently to decreased feed efficiency and growth in weaned pigs. Given that few studies have addressed the host-virus interaction in vivo, this study focused on endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in jejunal epithelial cells during PEDV infection. Eight-week-old pigs (n = 64) were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24) and analyzed for PEDV viral RNA shedding using reverse transcription-quantitative polymerase chain reaction and for viral antigen…

Kursi Wufarikun Ziyabit Improves the Physiological Changes by Regulating Endoplasmic Reticulum Stress in the Type 2 Diabetes db/db Mice.

Kursi Wufarikun Ziyabit (KWZ) is a classic traditional medicine used for the prevention treatment of diabetes in China. It was widely used a … creased. These results suggested that KWZ is effective for type 2 diabetes by improving endoplasmic reticulum (ER) stress in the liver of db/db mice, and it might prevent the damage of insulin Beta cells and alleviate insulin resistance.

CaMK II/Ca2+ dependent endoplasmic reticulum stress mediates apoptosis of hepatic stellate cells stimulated by transforming growth factor beta 1.

Previous studies by our group have demonstrated that the calcium imbalance in rat hepatic stellate cells (HSCs) can induce endoplasmic reticulum stress (ERS) and promote cell apoptosis. KN-62, an inhibitor of Calmodulin kinase II (CaMK II), can decrease the expression of CaMK II that plays a major role in regulating the steady state of intracellular Ca2+. Uridine triphosphate (UTP) plays a biological role in increasing indirectly the level of intracellular Ca2+. In the experiment, we demonstrate that KN-62 and UTP can inhibit the proliferation and promote the apoptosis in HSCs, increase the le…

Aggregative Perivascular Tumor Cell Growth Pattern of Primary Central Nervous System Lymphomas Is Associated with Hypoxia-Related Endoplasmic Reticulum Stress.

Primary central nervous system lymphomas (PCNSLs) often present a unique histopathological feature of aggregative perivascular tumor cells (APVT). Our previous studies showed that patients of PCNSL with APVTs exhibited poor long-term outcomes and increased expression of the endoplasmic reticulum stress (ERS) factor X-box-binding protein (XBP1). However, very little is known about molecular mechanism of the APVT formation in PCNSLs. The aim of this study is to determine if hypoxia-induced ERS is related to the APVT formation in PCNSLs. In this study, cell culture was used to observe the interpl…

IRE1α-XBP1 Affects the Mitochondrial Function of Aβ25-35-Treated SH-SY5Y Cells by Regulating Mitochondria-Associated Endoplasmic Reticulum Membranes.

Background: Neurotoxicity induced by the amyloid beta (Aβ) peptide is one of the most important pathological mechanisms of Alzheimer's disea … reased the expression and interaction of IP3R, Grp75, and vdac1 and led to an increased endoplasmic reticulum (ER)-mitochondria association, malfunction of mitochondria-associated ER-membranes (MAMs), and mitochondrial dysfunction. These deficits were rescued by inhibiting the IRE1α-XBP1 axis. Conclusion: These findings demonstrate that Aβ peptide induces t …

Interaction of nobiletin with methotrexate ameliorates 7-OH methotrexate-induced nephrotoxicity through endoplasmic reticulum stress-dependent PERK/CHOP signaling pathway.

Drug-induced nephrotoxicity is a frequent adverse event that contributes to acute kidney injury with tubular and/or glomerular lesions. Meth … se. RNA-seq analysis revealed that 7-OH MTX was mainly related to protein processing in endoplasmic reticulum (ER) stress, with the PERK/CHOP pathway selected as the most significant for metabolic nephrotoxicity. Meanwhile, the cross-linked proteins and conducted signals were investigated by western blotting and further verified by GSK inhibition analyses. …

Interactions between Endoplasmic Reticulum Stress and Autophagy: Implications for Apoptosis and Neuroplasticity-Related Proteins in Palmitic Acid-Treated Prefrontal Cells.

Lipotoxicity of palmitic acid (PA) or high-fat diets has been reported to increase endoplasmic reticulum (ER) stress and autophagy in peripheral tissue as well as apoptotic cell death. It also can lead to an AD-like pathological pattern. However, it has been unknown that PA-induced ER stress and autophagy are involved in the regulation of neuroplastic abnormalities. Here, we investigated the roles of ER stress and autophagy in apoptosis and neuroplasticity-related protein expression in PA-treated prefrontal cells. Prefrontal cells dissected from newborn Sprague-Dawley rats were treated with PA…

Lack of Associations between Endoplasmic Reticulum Aminopeptidase 2 Gene Polymorphisms and Ankylosing Spondylitis: A Meta-analysis with Trial Sequential Analysis.

BACKGROUND: Endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is reported to be associated with inflammation-related diseases. Several studies have investigated the associations of ERAP2 gene polymorphisms and susceptibility to ankylosing spondylitis (AS). However, the findings of those studies were inconsistent. The aim of this study was to elucidate the associations by a meta-analysis with trial sequential analysis (TSA). METHODS: Online databases of PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, and CNKI were searched to identify eligible studies on the associations of ERAP2 …