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  • Ire1
  • Upon dimerization and autophosphorylation, IRE1α splices XBP-1 mRNA, which adjusts the reading frame to allow translation of an active transcriptional factor XBP-1. (nih.gov)
  • pathways
  • Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. (nih.gov)
  • We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. (nih.gov)
  • It was reported that iron could modulate ER stress-associated pathways [ 16 - 19 ], and its chelators have been shown to inhibit the development of pulmonary vascular remodeling induced by hypoxia [ 20 ]. (ijbs.com)
  • These results indicate that the aging lung is more susceptible to injury and fibrosis associated with endoplasmic reticulum stress, apoptosis of type II lung epithelial cells, and activation of profibrotic pathways. (pubmedcentralcanada.ca)
  • eIF2
  • The overexpression of a C-terminal fragment of GADD34 that constitutively dephosphorylates eIF2α was able to attenuate the phosphorylation of eIF2α and severely inhibit the induction of ATF4 in response to hypoxic stress. (asm.org)
  • These studies demonstrate the essential role of ATF4 in the response to hypoxic stress, define the pathway for its induction, and reveal that GADD34, a target of ATF4 activation, negatively regulates the eIF2α-mediated inhibition of translation. (asm.org)
  • The splicing of XBP-1 mRNA and the level of phosphorylation of eIF2α, indicators of ER stress, significantly increased at early time points after M. bovis infection. (frontiersin.org)
  • AMPK
  • Using the human adult diploid RPE cell line ARPE-19, we demonstrated that both zeaxanthin and lutein could mimic the wolfberry preventive effect on activation of AMPK, thioredoxin, Mn SOD, FOXO3α activities, normalize cellular reactive oxygen species and attenuate ER stress in ARPE-19 cells exposed to a high glucose challenge. (nih.gov)
  • glucose
  • Since DN occurs in familial clusters, genetic factors may contribute to DN development although the incidence and severity of DN are affected by the extent of blood glucose status [ 3 , 4 ]. (hindawi.com)
  • The aim of the present study was to determine whether postburn metforminmediated glucose modulation reduces hepatic ER stress, alters hepatic metabolic marker expressions and improves function. (springer.com)
  • In the fed state, for example, activated PDC increases glucose oxidation for the provision of acetyl-CoA for the citric acid cycle, fatty acid synthesis, and cholesterol synthesis. (highwire.org)
  • Because the hypothalamus controls various aspects of peripheral metabolism, including appetite control, energy expenditure, carbohydrate/lipid metabolism, and blood pressure, recent studies aimed to investigate whether alleviating hypothalamic ER stress and inflammation could have a beneficial impact on whole-body metabolic control, e.g., regulating peripheral glucose homeostasis ( 15 ). (diabetesjournals.org)
  • Indeed, transient hypothalamic ER stress induces peripheral glucose intolerance and increases plasma levels of noradrenaline in mice, whereas central inhibition of brain ER stress by a chemical chaperone, tauroursodeoxycholic acid (TUDCA), partially reversed obesity-associated metabolic and blood pressure deregulation ( 16 ). (diabetesjournals.org)
  • macrophages
  • Using DNA microarray and network analyses of macrophages, they show compelling evidence that ATF4, which is involved in the ER stress response, plays an essential role in IL-6 expression induced by various metabolic stresses, including ER stress. (diabetesjournals.org)
  • 18 ) also suggest that ER-stressed macrophages may trigger autoimmune diseases through IL-6 production. (diabetesjournals.org)
  • metabolic
  • IL-6 has been shown to play crucial roles in insulin resistance and type 2 diabetes ( 19 ), raising the possibility that ATF4 signaling is a novel target for the treatment of metabolic diseases. (diabetesjournals.org)
  • Severe burn injury causes hepatic dysfunction that results in major metabolic derangements including insulin resistance and hyperglycemia and is associated with hepatic endoplasmic reticulum (ER) stress. (springer.com)
  • The aim of the present study is to determine the effects of metformin on postburn hepatic ER stress and metabolic markers. (springer.com)
  • Here, we summarize the state-of-the-art evidence supporting the possibility that adverse metabolic postnatal outcomes such as IR in the offspring of pregnancies with MO and/or excessive GWG may be related to intrauterine activation of ER stress response. (hindawi.com)
  • guanine nucleo
  • UPR was triggered by knockdown of Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF-1) or the GBF-1 inhibitor golgicide A (GCA) and stimulated HAdV infection. (asm.org)
  • Liang Y, Morozova N, Tokarev AA, Mulholland JW, Segev N (2007) The role of Trs65 in the Ypt/Rab guanine nucleotide exchange factor function of the TRAPP II complex. (springer.com)
  • modifiable risk factors
  • In addition to conventional modifiable risk factors (hypertension, smoking, hyperlipidemia, and hemodynamic changes), hereditary components are also considered to be a significant risk factor for DN. (hindawi.com)
  • while articular overload, intense physical activity, and obesity are modifiable risk factors. (hindawi.com)
  • response
  • The prosurvival and proapoptotic phases of the ER stress response. (ahajournals.org)
  • The steps involved in the prosurvival (blue steps 1 to 6) and proapoptotic phases (red steps 5′ to 8′) of the ER stress response are shown. (ahajournals.org)
  • In general, during the prosurvival phase, components of the rapidly activated ER stress response contribute to restoring the ER luminal environment and resolving the ER stress, thus promoting survival. (ahajournals.org)
  • However, if the ER stress is not resolved during the prosurvival phase, components of the ER stress response activated at later stages, during the proapoptotic phase, initiate the programmed cell death pathway. (ahajournals.org)
  • The ER stress response is a highly conserved signaling system that has been studied in many different cell and tissue types. (ahajournals.org)
  • Other mechanisms of gene regulation are important to the cellular response to stress, such as the control of translation initiation. (asm.org)
  • In this study, the role of alcohol-induced endoplasmic reticulum (ER) stress response in liver cancer development was investigated using an animal model with a liver knockout (KO) of the chaperone BiP and under constitutive hepatic ER stress. (frontiersin.org)
  • Long-term alcohol and high fat diet feeding resulted in higher levels of serum alanine aminotransferase, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months) KO females than in either middle-aged (6 months) KOs or older (aged 16 months) wild type females. (frontiersin.org)
  • Activating transcription factor 3 (ATF3) belongs to the ATF/cyclic AMP responsive element binding family of transcription factors and is often described as an adaptive response gene whose activity is usually regulated by stressful stimuli. (frontiersin.org)
  • One factor that contributes to the successful regeneration of the axons in peripheral nerves is the complex cell body response the neurons show to axotomy. (frontiersin.org)
  • In relation to the results above, overexpression of transcripts involved with response to cellular stress was highly statistically significant after treatment with black cohosh extract. (nih.gov)
  • Endoplasmic reticulum (ER) stress, a feature of many conditions associated with pulmonary hypertension (PH), is increasingly recognized as a common response to promote proliferation in the walls of pulmonary arteries. (ijbs.com)
  • Treatment human PASMCs with FeSO4 induced the similar ER stress and proliferation response and iron chelator (deferoxamine) abrogated the ER stress and proliferation induced by Lcn2 in cultured human PASMCs. (ijbs.com)
  • upregulates
  • In addition, burn injury upregulates hepatic ER stress ( 6 , 7 ), causing hepatic damage that can be detrimental to recovery. (springer.com)
  • plays a pivotal role
  • Hypoxic stress plays a pivotal role in normal human development and physiology, including embryogenesis and wound repair, and has been well studied for its importance in the pathogenesis of several human diseases, namely, heart disease, stroke, diabetes, and cancer (for a detailed review, see reference 52 ). (asm.org)
  • gene expression
  • The importance of translational control on gene expression was originally proposed to play a fundamental role during development ( 47 ) and has subsequently been proven critical in regulating numerous physiological processes in the cell, including growth stimulation ( 39 ), cell cycle progression ( 48 ), differentiation ( 55 ), endoplasmic reticulum (ER) stress, ( 17 ), and oncogenic signaling in cancer ( 46 ). (asm.org)
  • Of the transcription factors that regulate these changes in gene expression, the function of c-Jun is the best understood. (frontiersin.org)
  • pathogenesis
  • This is a warning sign for healthcare systems to be vigilant not only for adequate management but also for identifying risk factors involved in the pathogenesis of DN. (hindawi.com)
  • signals
  • Soon after cells are subjected to environmental conditions that perturb the ER environment, including ischemia, the ER signals to other cellular systems in a collaborative effort to resolve the ER stress and to survive ( Figure 1 , steps 2 to 4, blue). (ahajournals.org)
  • Recent studies have uncovered critical factors responsible for the cross-talk of apoptotic signals between the ER and mitochondria by identifying associations between BAP31 and mitochondrial fission factor (Fis1) and Bcl-2 ( 13 - 15 ). (sciencemag.org)
  • membrane
  • GBF-1 is a GEF for ADP ribosylation factors (Arfs) regulating endoplasmic reticulum (ER)-to-Golgi apparatus and intra-Golgi apparatus membrane transport. (asm.org)
  • specifically, the ER comprises large membrane-bound compartments, with a network extending throughout the cytoplasm and a membrane subdomain, the mitochondria-associated ER membrane (MAM), which is a highly conserved feature of eukaryotic cells, and appears to be in close contact with the mitochondria ( 6 , 7 ). (sciencemag.org)