Abstract:
:Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4 (G protein-coupled receptor 4) is a member of the proton-sensing G protein-coupled receptors and it has high expression in endothelial cells (ECs). We have previously reported that acidosis induces a broad inflammatory response in ECs. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress response genes such as CHOP (C/EBP homologous protein) and ATF3 (activating transcription factor 3). In the current study, we have examined acidosis/GPR4- induced ER stress pathways in human umbilical vein endothelial cells (HUVEC) and other types of ECs. All three arms of the ER stress/unfolded protein response (UPR) pathways were activated by acidosis in ECs as an increased expression of phosphorylated eIF2α (eukaryotic initiation factor 2α), phosphorylated IRE1α (inositol-requiring enzyme 1α), and cleaved ATF6 upon acidic pH treatment was observed. The expression of other downstream mediators of the UPR, such as ATF4, ATF3, and spliced XBP-1 (X box-binding protein 1), was also induced by acidosis. Through genetic and pharmacological approaches to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in ECs may regulate vascular growth and inflammatory response in the acidic microenvironment.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Dong L,Krewson EA,Yang LVdoi
10.3390/ijms18020278subject
Has Abstractpub_date
2017-01-27 00:00:00issue
2issn
1422-0067pii
ijms18020278journal_volume
18pub_type
杂志文章abstract::Non-communicable diseases (NCDs) have become the largest contributor to worldwide morbidity and mortality. Among them, cancer and cardiovascular diseases (CVDs) are responsible for a 47% of worldwide mortality. In general, preventive approaches modifying lifestyle are more cost-effective than treatments after disease ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19082305
更新日期:2018-08-06 00:00:00
abstract::The physiological function of Arabidopsis thaliana universal stress protein (AtUSP) in plant has remained unclear. Thus, we report here the functional role of the Arabidopsis universal stress protein, AtUSP (At3g53990). To determine how AtUSP affects physiological responses towards cold stress, AtUSP overexpression (A...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18122546
更新日期:2017-11-27 00:00:00
abstract::An economical and environmentally friendly whey protein fractionation process was developed using supercritical carbon dioxide (sCO(2)) as an acid to produce enriched fractions of α-lactalbumin (α-LA) and β-lactoglobulin (β-LG) from a commercial whey protein isolate (WPI) containing 20% α-LA and 55% β-LG, through sele...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13010240
更新日期:2012-01-01 00:00:00
abstract::The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20020455
更新日期:2019-01-21 00:00:00
abstract::Biofilms are a multicellular way of life, where bacterial cells are close together and embedded in a hydrated macromolecular matrix which offers a number of advantages to the cells. Extracellular polysaccharides play an important role in matrix setup and maintenance. A water-insoluble polysaccharide was isolated and p...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21051702
更新日期:2020-03-02 00:00:00
abstract::Shellfish allergy affects 2% of the world's population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among shellfis...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22010032
更新日期:2020-12-22 00:00:00
abstract::The aim of this study was to explore the optimal therapeutic dose and time window of picroside II for treating cerebral ischemic injury in rats according to the orthogonal test. The middle cerebral artery occlusion (MCAO) models were established by intraluminally inserting a thread into middle cerebral artery (MCA) fr...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13032551
更新日期:2012-01-01 00:00:00
abstract::Cell adhesion ability is one of the components to establish cell organization and shows a great contribution to human body construction consisting of various types of cells mixture to orchestrate tissue specific function. The cell adhesion molecule 1 (CADM1) is a molecule of cell adhesion with multiple functions and h...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21249732
更新日期:2020-12-20 00:00:00
abstract::Docking-i.e., interaction of a small molecule (ligand) with a proteic structure (receptor)-represents the ground of drug action mechanism of the vast majority of bioactive chemicals. Ligand and receptor accommodate their geometry and energy, within this interaction, in the benefit of receptor-ligand complex. In an ind...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18071377
更新日期:2017-06-27 00:00:00
abstract::CD4+T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-naïve RA patient...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21186847
更新日期:2020-09-18 00:00:00
abstract::A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a-e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a-e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammat...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms15045821
更新日期:2014-04-04 00:00:00
abstract::Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malar...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20225574
更新日期:2019-11-08 00:00:00
abstract::Rice (Oryza sativa L.) is a widely cultivated food crop around the world, especially in Asia. However, rice seedlings often suffer from cold stress, which affects their growth and yield. Here, RNA-seq analysis and Meta-QTLs mapping were performed to understand the molecular mechanisms underlying cold tolerance in the ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21134615
更新日期:2020-06-29 00:00:00
abstract::Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms17040490
更新日期:2016-04-02 00:00:00
abstract::Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, e...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21239281
更新日期:2020-12-05 00:00:00
abstract::Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular menisc...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20051120
更新日期:2019-03-05 00:00:00
abstract::Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral res...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17071125
更新日期:2016-07-14 00:00:00
abstract::RNAi technology has significant potential as a future therapeutic and could theoretically be used to knock down disease-specific RNAs. However, due to frequent off-target effects, low efficiency, and limited accessibility of nuclear transcripts, the clinical application of the technology remains challenging. In this s...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21238904
更新日期:2020-11-24 00:00:00
abstract::Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21093144
更新日期:2020-04-29 00:00:00
abstract::Reduced forms of ascorbate (AsA) and glutathione (GSH) are among the most important non-enzymatic foliar antioxidants in maize (Zea mays L.). The survey was aimed to evaluate impact of bird cherry-oat aphid (Rhopalosiphum padi L.) or grain aphid (Sitobion avenae F.) herbivory on expression of genes related to ascorbat...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17030268
更新日期:2016-02-23 00:00:00
abstract::Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22020596
更新日期:2021-01-09 00:00:00
abstract::Plant regeneration and somatic embryogenesis through interspecific hybridization among different Carica species were studied for the development of a papaya ringspot virus-resistant variety. The maximum fruit sets were recorded from the cross of the native variety C. papaya cv. Shahi with the wild species C. cauliflor...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms131217065
更新日期:2012-12-12 00:00:00
abstract::Over the years, there have been many developments and advances in the field of integral membrane protein research. As important pharmaceutical targets, it is paramount to understand the mechanisms of action that govern their structure-function relationships. However, the study of integral membrane proteins is still in...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20102605
更新日期:2019-05-27 00:00:00
abstract::Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatri...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms17040461
更新日期:2016-03-29 00:00:00
abstract::Arrhythmias in Brugada syndrome patients originate in the right ventricular outflow tract (RVOT). Over the past few decades, the characterization of the unique anatomy and electrophysiology of the RVOT has revealed the arrhythmogenic nature of this region. However, the mechanisms that drive arrhythmias in Brugada synd...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21197051
更新日期:2020-09-25 00:00:00
abstract::The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal inject...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21228628
更新日期:2020-11-16 00:00:00
abstract::Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21207585
更新日期:2020-10-14 00:00:00
abstract::The mushroom Inonotus obliquus has been widely used as a folk medicine in Russia, Poland and most of the Baltic countries. In this study, water-soluble and alkali-soluble crude polysaccharides (IOW and IOA) were isolated from I. obliquus, and the carbohydrate-rich fractions IOW-1 and IOA-1 were obtained respectively a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13079194
更新日期:2012-01-01 00:00:00
abstract::Recent studies have demonstrated that exosomal microRNAs (miRNAs) have the potential of facilitating molecular diagnosis. Currently, little is known about the underlying mechanism behind late-onset acute graft-versus-host disease (LA GVHD). Identifying differentially expressed miRNAs in exosomes should be useful for u...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19092493
更新日期:2018-08-23 00:00:00
abstract::Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18040859
更新日期:2017-04-19 00:00:00