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Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways Involved in the Health-Promoting Effects of Allicin on the Jejunum.

Intestinal endoplasmic reticulum stress (ERS) triggered by adverse factors disturbs the normal function of the intestine. Allicin has been reported to promote intestinal health and development. In the present study, we established in vivo (35-day-old weaned piglets, 4-week-old mice) and in vitro (IPEC-J2 cell line) ERS models to explore the possible mechanisms by which allicin may benefit intestinal health. This study revealed the following: (1) allicin supplementation improved intestinal morphological indices and ameliorated mild ERS in the jejunum of the weaned piglets; (2) allicin supplemen

Whole exome sequencing implicates eye development, the unfolded protein response and plasma membrane homeostasis in primary open-angle glaucoma.

PURPOSE: To identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by an … to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = 7.72×10-5, corrected p = 0.013). The UPR is known to be involved in myocilin-related glaucoma; our results suggest the UPR has a role in non-myocilin causes of HTG. NTG cases showed enrichment in ion channel transport processes (p = 1.05× …

Regulated IRE1-dependent decay pathway is activated during Japanese encephalitis virus-induced unfolded protein response and benefits viral replication.

Japanese encephalitis virus (JEV) infection-induced encephalitis causes extensive death or long-term neurological damage, especially among children, in south and south-east Asia. Infection of mammalian cells has shown induction of an unfolded protein response (UPR), presumably leading to programmed cell death or apoptosis of the host cells. UPR, a cellular response to accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen, is initiated by three ER-lumen-resident sensors (PERK, IRE1 and ATF6), and involves transcriptional and translational regulation of the expre…

Pharmacological modulation of the retinal unfolded protein response in Bardet-Biedl syndrome reduces apoptosis and preserves light detection ability.

Ciliopathies, a class of rare genetic disorders, present often with retinal degeneration caused by protein transport defects between the inn … ts in protein retention in the endoplasmic reticulum. The protein overload activates a proapoptotic unfolded protein response leading to a specific Caspase12-mediated death of the photoreceptors. Having identified a therapeutic window in the early postnatal retinal development and through optimized pharmacological modulation of the unfolded protein response, combining thre …

Disease-related amyloidogenic variants of human lysozyme trigger the unfolded protein response and disturb eye development in Drosophila melanogaster.

We have created a Drosophila model of lysozyme amyloidosis to investigate the in vivo behavior of disease-associated variants. To achieve th … anning electron microscopy for eye phenotype classification, and immunohistochemistry to detect the unfolded protein response (UPR) activation. We observed that expressing the destabilized F57I and D67H lysozymes triggers UPR activation, resulting in degradation of these variants, whereas the WT lysozyme is secreted into the fly hemolymph. Indeed, the level of WT was up to …

Модуляция развернутой реакции белка с помощью C-терминального фрагмента MANF облегчает восстановление в моделях множественного склероза.

Воспаление в множестве склероза ведет к хронической активации механизма клеточного стресса, развернутой реакции белка (УПО), которая, как считается, усиливает нейроинфламмацию и предотвращает регенеративную реакцию тканей, например ремиилизацию. Модифицирующийся в рамках УПО белковый MANF продемонстрировал большие перспективы для смягчения хронической активации УПО и усиления регенерации тканей в различных моделях заболеваний, но не достигает CNS, когда он предоставляется в периферии. Мы использовали C-MANF, C-терминальный фрагмент MANF, и показали, что подкожное управление C-MANF способствова

Совпадение в аннотации оригинала
Inflammation in multiple sclerosis leads to chronic activation of a cellular stress mechanism, the unfolded protein response (UPR), which is thought to both exacerbate neuroinflammation and prevent regenerative tissue responses such as remyelination. The UPR-modulating protein MANF has shown great promise for attenuating chronic UPR activation and enhancing …

Unfolded protein response modulates the effects of GHRH antagonists in experimental models of in vivo and in vitro lung injury.

The development of efficient targeted therapies to ameliorate endothelial disorders is of the utmost need, as evident by the devastating outcomes of the recent pandemic. Recent findings suggest that unfolded protein response (UPR) modulates barrier function. In the current study, we reveal that the aforementioned highly conservative mechanism is involved in the protective effects of growth hormone-releasing hormone antagonists (GHRHAnt) in lung injury, both in vivo and in vitro. In bovine pulmonary artery endothelial cells, UPR suppression counteracted the protective effects of GHRHAnt in lipo…

Elevated homocysteine activates unfolded protein responses and causes aberrant trophoblast differentiation and mouse blastocyst development.

Hyperhomocysteinemia may arise from folate/vitamin B12 deficiency, genetic polymorphisms, kidney disease, or hypothyroidism. It is associate … l line. Both effects diminish the stem cell pool, and are mediated in an endoplasmic reticulum (ER) unfolded protein response (UPRER )-dependent manner. Targeted alleviation of UPRER may therefore provide a new therapeutic intervention to improve pregnancy outcome in women with hyperhomocysteinemia.

Carnosic acid promotes degradation of the androgen receptor and is regulated by the unfolded protein response pathway in vitro and in vivo.

Androgen deprivation therapy in prostate cancer is extremely effective; however, due to the continuous expression and/or mutagenesis of andr … dation is dependent on ER stress pathway. Future studies will need to evaluate other aspects of the unfolded protein response pathway to characterize the regulation of AR degradation. Furthermore, cotreating cells individually with carnosic acid and proteasome inhibitor (MG-132) and carnosic acid and an ER stress modulator (salubrinal) restored protein levels of AR, sugges …

Yip1A, a novel host factor for the activation of the IRE1 pathway of the unfolded protein response during Brucella infection.

Brucella species replicate within host cells in the form of endoplasmic reticulum (ER)-derived vacuoles. The mechanisms by which the bacteria are sequestered into such vacuoles and obtain a continuous membrane supply for their replication remain to be elucidated. In the present study, we provided several lines of evidence that demonstrate the mechanism by which B. abortus acquires the ER-derived membrane. First, during Brucella infection, the IRE1 pathway, but not the PERK and ATF6 pathways, of the unfolded protein response (UPR) was activated in a time-dependent manner, and the COPII vesicle …

BMAL1 modulation alleviates inflammatory responses in monocytes by targeting the Fis1-mediated mitochondrial unfolded protein response in high-altitude hypoxia.

BACKGROUND: Hypoxia-induced inflammation has been implicated in the progression of high-altitude illnesses. Mitochondria are key organelles … eceptor protein 3 inflammasome activation in monocytes by targeting the Fis1-mediated mitochondrial unfolded protein response. Basic helix-loop-helix family member E40, a hypoxic stress-responsive transcription factor, directly promoted Bmal1 transcription and triggered inflammation in monocytes. In contrast, myeloid-specific deletion of BMAL1 alleviated the inflammatory a …

The unfolded protein response element IRE1α senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling.

The plasma membrane and all membrane-bound organelles except for the Golgi and endoplasmic reticulum (ER) are equipped with pattern-recognition molecules to sense microbes or their products and induce innate immunity for host defense. Here, we report that inositol-requiring-1α (IRE1α), an ER protein that signals in the unfolded protein response (UPR), is activated to induce inflammation by binding a portion of cholera toxin as it co-opts the ER to cause disease. Other known UPR transducers, including the IRE1α-dependent transcription factor XBP1, are dispensable for this signaling. The inflamm…

Exosomal misfolded α1-antitrypsin triggers a cytosolic GRP78-dependent unfolded protein response and pro-survival signaling in pre-metastatic tissues.

Tumor-derived exosomes (TDEs) promote cancer progression by transmitting oncogenic signals to adjacent cells. However, their impact on dista … prospective sites for metastasis, induces cytoplasmic expression of GRP78, triggers a pro-survival unfolded protein response (UPR), activates proliferation and inflammation, while suppressing apoptosis, both in vitro and in vivo. In silico modeling and co-immunoprecipitation confirm interaction between GRP78 and mA1AT, implicating non-canonical UPR activation. Depletion o …

African swine fever virus MGF_110-8L promotes host cell autophagy and suppresses interferon signaling by activating the unfolded protein response.

African swine fever virus (ASFV) infection induces cellular stress that activates the unfolded protein response (UPR), a key pathway for restoring endoplasmic reticulum (ER) homeostasis. However, the mechanisms by which ASFV modulates the UPR remain incompletely understood. Here, we identify the ASFV protein MGF_110-8L as a key regulator of the UPR, leading to the dissociation and activation of the UPR sensors PERK, IRE1α, and ATF6, which subsequently restore ER homeostasis. Moreover, MGF_110-8L triggers UPR-dependent autophagy, which in turn contributes to the suppression of type I interferon…

Control of Intestinal Type 3 Immunity by the Unfolded Protein Response Sensor Inositol-Requiring Enzyme 1α in Antigen-Presenting Cells.

BACKGROUND & AIMS: The unfolded protein response is an essential cellular program maintaining intestinal homeostasis by acting on several cell types. However, whether the unfolded protein response sensor inositol-requiring enzyme 1α acts on dendritic cells and other antigen-presenting cells for shaping intestinal immunity remains poorly defined. METHODS: Here, we dissect the role of the endoribonuclease domain of the unfolded protein response sensor inositol-requiring enzyme 1α in intestinal CD11c+ antigen-presenting cells, using inositol-requiring enzyme 1α endoribonuclease reporter mice and…

Membranal Expression of Calreticulin Induced by Unfolded Protein Response in Melanocytes: A Mechanism Underlying Oxidative Stress-Induced Autoimmunity in Vitiligo.

Calreticulin (CRT), a damage-associated molecular pattern molecule, is reported to translocate from the endoplasmic reticulum to the membrane in melanocytes under oxidative stress. To investigate the potential role of CRT in the pathogenesis of vitiligo, we analyzed the correlation between CRT and ROS in serum and lesions of vitiligo, detected CRT and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression in vitiligo lesions, and studied the production of CRT and mediators of unfolded protein response (UPR) pathway and then tested the chemotactic migration of CD8+ T cells or CD…

Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Preeclampsia-Induced Apoptosis of Placental Trophoblastic Cells Via Inhibiting the Mitochondrial Unfolded Protein Response.

Preeclampsia is a serious obstetric complication. Currently, there is a lack of effective preventive approaches for this disease. Recent studies have identified transcutaneous auricular vagus nerve stimulation (taVNS) as a potential novel non-pharmaceutical therapeutic modality for preeclampsia. In this study, we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt. Our results showed that taVNS promoted the release of acetylcholine (ACh). ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS (mtROS), presumab

The small compound Icerguastat reduces muscle defects in oculopharyngeal muscular dystrophy through the PERK pathway of the unfolded protein response.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease characterized by the progressive degeneration of specific muscles. OPMD is due to a mutation in the gene encoding poly(A) binding protein nuclear 1 (PABPN1) leading to a stretch of 11 to 18 alanines at N-terminus of the protein, instead of 10 alanines in the normal protein. This alanine tract extension induces the misfolding and aggregation of PABPN1 in muscle nuclei. Here, using Drosophila OPMD models, we show that the unfolded protein response (UPR) is activated in OPMD upon endoplasmic reticulum stress. Mutations in …

Unfolded protein response-induced expression of long noncoding RNA Ngrl1 supports peripheral axon regeneration by activating the PI3K-Akt pathway.

In mammals, long noncoding RNA (LncRNA) contributes to neuronal development and injury repair mediated by the spatiotemporal regulation of gene expression. However, the pivotal role of lncRNA in intrinsic axon regeneration control following a nerve injury remains unknown. In this article, we report a neurite growth-related lncRNA termed Ngrl1, which supported peripheral axon regeneration post sciatic nerve crush (SNC). A rapid increase in Ngrl1 expression was detected following SNC, and knockdown of Ngrl1 impaired axon regeneration both in vitro and in vivo. The unfolded protein response (i.e.…

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…