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Activation of HSPA5 contributes to pazopanib-induced hepatotoxicity through l-ornithine metabolism pathway and endoplasmic reticulum stress.

OBJECTIVES: The clinical application of Pazopanib (Paz) is often accompanied by hepatotoxicity. However, the mechanisms of hepatic toxicity … d L02 cells cell viability in a dose-dependent manner. We also discovered activation of endoplasmic reticulum stress, apoptosis, and autophagy in Paz-treated L02 cells, as evidenced by the boosted expression of HSPA5, p-IRE1α, ATF4, ATF6, p-eIF2α, LC3, Beclin-1, and a decrease of phosphorylated PI3K, AKT, and mTOR levels. Moreover, 4-PBA, l-ornithine, and H …

Letter to editor: SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer.

We are writing to commend the recent article by Zhuang et al. titled "SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer," published in the Journal of Translational Medicine. This is a highly innovative and clinically significant article that seamlessly integrates bioinformatics and functional analysis to identify SIGMAR1 as a key regulator of endoplasmic reticulum (ER) stress in bladder cancer (BC). Additionally, it establishes a GPCR-tumor microenvironment (TME) classification system combining 15 GPCRs and five immune cell types, offering a…

Endoplasmic reticulum stress regulates swainsonine-induced the autophagy in renal tubular epithelial cells through UPR signaling pathway.

Swainsonine (SW), the primary toxic component of locoweed, induces toxic response in grazing livestock. The swainsonine induced toxicity is characterized by symptoms including head tremors, ataxia, and limb paralysis. The mechanisms of the toxicity remained to be investigated. The unfolded protein response (UPR) plays a key role in alleviating endoplasmic reticulum stress (ERS) by reducing protein synthesis and promoting the degradation of misfolded proteins. ERS is closely associated with both the UPR and autophagy activation. However, the involvement of the UPR signaling pathway in SW-induce…

Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by a decline in cognitive, learning, and memory abilities. Neuroinflammation is associ … cadian rhythm on AD was discussed, and we also analysed the effects of inflammation and endoplasmic reticulum stress (ERS) induced by lipid abnormalities on intestinal mucosal barrier and neurodegeneration; furthermore, the importance of lipid homeostasis (phospholipids, fatty acids, sterol) in maintaining the functions of endoplasmic reticulum was emphasiz …

Endurance Training Alleviates Metabolic-Associated Fatty-Liver Disease (MAFLD)-Related Testicular Impairments via Endoplasmic Reticulum Stress Regulation.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD), the most prevalent liver disorder globally, affects 20%-40% of the population and presents significant health challenges. Studies link MAFLD to male reproductive dysfunction, highlighting the need for effective interventions. This study investigates the impact of MAFLD on testicular function and evaluates the protective role of endurance training, with a focus on the GRP78-IRE-1α-ATF6 signaling pathway. METHODS: Forty-four rats were allocated into two dietary groups (n = 22 each): a standard diet control group (C) and a high-fat di

Mechanism of Shenzhu components in alleviating chemotherapy-induced diarrhea via mitochondria-associated endoplasmic reticulum membranes (MAMs) regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy-induced diarrhea (CID) is a common side effect of 5-fluorouracil (5-FU). Traditional Chinese me … oil (AMO) and Panax ginseng total saponins (PGS) (AP) regulated mitochondria-associated endoplasmic reticulum membranes (MAMs) to restore intestinal barrier function in CID. METHODS: A 5-FU-induced CID mouse model was used to evaluate the effects of AP on diarrhea scores and body weight. Hematoxylin-eosin (HE) staining was used to examine colon pathologica …

Icaritin induces paraptosis in hepatocellular carcinoma cells by targeting BHLHE40 via endoplasmic reticulum stress and mitochondrial dysfunction.

OBJECTIVE: Icaritin, a flavonoid derived from the traditional Chinese medicine Epimedium, exhibits diverse biological activities; however, t … . ABBREVIATIONS: HCC: Hepatocellular carcinoma; TCM: Traditional Chinese Medicine; ER: Endoplasmic Reticulum; MMP: Mitochondrial Membrane Potential; ROS: Reactive Oxygen Species; CTG: CellTiter-Glo; EdU: 5-ethynyl-2'-deoxyuridine; UPR: Unfolded Protein Response; BHLHE40: Basic helix-loop-helix family member E40; IPA: Ingenuity Pathway Analysis; CETSA: Cell …

Anxa10 and neuropathic pain: Insights into dysregulation of endoplasmic reticulum-mitochondria contact tethering complex and therapeutic potential.

The stability of membrane contact sites is critically dependent on Endoplasmic Reticulum mitochondria contact tethering complexes (EMCTCs), and dysregulation of these sites has been implicated in neuropathic diseases. In this study, we examined the role of Annexin A10 (Anxa10), a calcium-dependent protein, in neuropathic pain by investigating its influence on EMCTCs dysregulation. Using RNA sequencing, western blotting, and behavioral assays, we observed that spared nerve injury (SNI)-induced neuropathic pain significantly increased Anxa10 expression levels within the spinal dorsal horn (SDH) …

Mitochondrial Tumor Suppressor 1A Attenuates Myocardial Infarction Injury by Maintaining the Coupling Between Mitochondria and Endoplasmic Reticulum.

BACKGROUND: Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)-mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions. …

Exogenous hydrogen sulfide improves non-alcoholic fatty liver disease by inhibiting endoplasmic reticulum stress/NLRP3 inflammasome pathway.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its exact pathogenesis has not been fully studied … lleviated lipid accumulation, inflammation, apoptosis and pyroptosis, and downregulated endoplasmic reticulum (ER) stress and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NRRP3) inflammasome in NAFLD. The activation of NLRP3 inflammasome weakened NaHS improvement of NAFLD, indicating that exogenous H2S ameliorated NAFLD …

Inner Ear Pathologies After Cochlear Implantation in Guinea Pigs: Functional, Histopathological, and Endoplasmic Reticulum Stress-Mediated Apoptosis.

OBJECTIVES: Vestibular dysfunction is one of the most common complications of cochlear implantation (CI); however, the pathological changes and mechanisms underlying inner ear damage post-CI remain poorly understood. This study aimed to investigate the functional and histopathological changes in the cochlea and vestibule as well as endoplasmic reticulum (ER) stress-mediated apoptosis in guinea pigs after CI. DESIGN: Auditory brainstem response, ice water test, and vestibular evoked myogenic potentials were used to assess cochlear and vestibular function in guinea pigs before and after CI. His…

Astragaloside VI attenuates mechanical stress-induced cardiac remodeling through piezo1-VDAC1 dependent endoplasmic reticulum unfolded protein response.

BACKGROUND: The dysregulation of protein homeostasis is a condition associated with mechanical stress-induced cardiac remodeling (CR) due to endoplasmic reticulum (ER) dysfunction and stress. PURPOSE: This research explores the effect of Piezo1 on the ER unfolded protein response (UPR) in cardiomyocytes following hypoxic stress, specifically through its interaction with VDAC1. In addition, the study evaluates the therapeutic potential that this mechanism holds for treating CR and cardiomyocyte hypertrophy. STUDY DESIGN: Considering the relative limitation of potential therapeutic drugs for C…

Chymotrypsin B2 (CTRB2) Deletion Variant Induces Endoplasmic Reticulum Stress but does not Increase Risk for Chronic Pancreatitis.

OBJECTIVES: CTRB2-del, a commonly occurring loss-of-function deletion variant in the CTRB2 gene encoding chymotrypsinogen B2 was shown to induce endoplasmic reticulum (ER) stress and increase risk for pancreatic cancer but not for chronic pancreatitis (CP). Since other digestive enzyme variants that cause misfolding and induce ER stress are strong risk factors for CP, the lack of association between CP and the CTRB2-del variant is surprising. The aim of the present study was to re-examine the biochemical and clinical characteristics of the CTRB2-del variant. METHODS: We performed experiments …

Митохондрийская эндоплазмическая ретикулумная мембрана и ионный обмен кальция: новое направление для старения и нейродегенеративных заболеваний.

Митохондрийские эндоплазмические ретикулумные мембраны служат важнейшими сигнальными узлами, координирующими связь между эндоплазмическим ретикулумом и митохондрией, и играют центральную роль в ионном обмене кальциями. Этот динамический интерфейс регулирует ключевые клеточные процессы, включая биоэнергетический метаболизм, апоптоз, автофагию и реакцию на стресс. Регулирование переноса кальция, связанного с митохондрией эндоплазмической ретикулумной мембраной, может нарушить внутриклеточный гомеостаз, что приводит к дисфункции митохондриала, окислительному стрессу и нейрональной смерти, которые

Совпадение в аннотации оригинала
Mitochondria-associated endoplasmic reticulum membranes serve as crucial signaling hubs mediating communication between the endoplasmic reticulum and mitochondria, and play a central role in calcium ion exchange. This dynamic interface regulates key cellular processes including bioenergetic metabolism, apoptosis, autophagy, and stress responses. Dysregulatio…

Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: potential targets for neural repair in neurological diseases.

The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels. Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane, formed by various proteins and protein complexes. This microstructural domain mediates several specialized functions, including calcium (Ca 2+ ) signaling, autophagy, mitochondrial morphology, oxidative stress response, and apoptosis. Notably, the dysregulation of Ca 2+ signal…

Rotenone-induced cell apoptosis via endoplasmic reticulum stress and PERK-eIF2α-CHOP signalling pathways in TM3 cells.

Rotenone (ROT), a widely used natural pesticide, has an uncertain effect on reproductive toxicity. In this study, we used 20 mice distributed randomly into four groups, with each group receiving ROT doses of 0, 2, 4, and 8 mg/kg/day for 28 days. The results demonstrated that ROT induced significant testicular damage, including impaired spermatogenesis, inhibition of testosterone synthesis, and apoptosis of Leydig cells. Additionally, ROT disrupted the normal ultrastructure of the endoplasmic reticulum (ER) in testicular tissue, leading to ER stress in Leydig cells. To further explore whether R…

Interleukin-38 alleviates hepatic steatosis through AMPK/autophagy-mediated suppression of endoplasmic reticulum stress in obesity models.

Interleukin-38 (IL-38), recently recognized as a cytokine with anti-inflammatory properties that mitigate type 2 diabetes, has been associated with indicators of insulin resistance and nonalcoholic fatty liver disease (NAFLD). This study investigated the impact of IL-38 on hepatic lipid metabolism and endoplasmic reticulum (ER) stress. We assessed protein expression levels using Western blot analysis, while monodansylcadaverine staining was employed to detect autophagosomes in hepatocytes. Oil red O staining was utilized to examine lipid deposition. The study revealed elevated serum IL-38 leve…

Chlorogenic acid ameliorates intestinal inflammation by inhibiting NF-κB and endoplasmic reticulum stress in lipopolysaccharide-challenged broilers.

Intestinal inflammation is a primary contributor to poor growth performance during poultry production. Chlorogenic acid (CGA) is a natural p … A toward intestinal inflammation and apoptosis appeared to be correlated with inhibited endoplasmic reticulum (ER) stress (P < 0.05). In summary, CGA supplementation improved intestinal morphology and integrity by inhibiting TLR4/NF-κB and ER stress pathways, which potentially reduced oxidative stress and inflammation, and ultimately improved the growth per …

Licochalcone A Ameliorates Cognitive Dysfunction in an Alzheimer's Disease Model by Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.

BackgroundEndoplasmic reticulum (ER) stress-induced neurodegeneration has been considered an underlying cause of Alzheimer disease (AD). Here, we investigated the beneficial effects of licochalcone A (Lico A), a valuable flavonoid of the root of the Glycyrrhiza species, against cognitive impairment in AD by regulating ER stress.MethodsThe triple transgenic mouse AD models were used and were administrated 5 or 15 mg/kg Lico A. Cognitive deficits, Aβ deposition, ER stress, and neuronal apoptosis were determined using Morris Water Maze test, probe trial, immunofluorescence staining, western blott…

The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress-related organ damage.

The anticancer, antioxidant, and immunomodulatory properties of carotenoids from saffron or apocarotenoids (e.g., crocin, safranal, crocetin, and picrocrocin) have prompted research into their benefits. Apocarotenoids seem to be effective compound for the treatment of chronic diseases, such as neurodegenerative, cardiovascular, cancer, respiratory, and metabolic disorders. Endoplasmic reticulum (ER) is an essential organelle found in the cytoplasm of eukaryotic cells that participates in the biosynthesis of proteins, lipids, and steroid hormones. Given the role of the ER in the regulation of s…