Protein disulfide isomerases (PDIs) aid protein folding and assembly by catalyzing formation shuffling of cysteine bonds in the endoplasmic reticulum (ER). Many members PDI family are expressed mammals, but roles specific PDIs vivo poorly understood. A recent homology-based search for additional identified anterior gradient homolog 2 (AGR2), a originally presumed to be secreted intestinal epithelial cells. Here, we show that AGR2 is present within ER secretory cells essential production...

Plasmin is converted from its zymogen plasminogen by tissue type or urokinase activator (PA) and degrades many components of the extracellular matrix (ECM). To explore possibility that PA-plasmin system regulates synaptic plasticity, we investigated effect plasmin on degradation ECM plasticity using organotypic hippocampal cultures. High-frequency stimulation produced long-term potentiation (LTP) in control slices, whereas was induced but not maintained slices pretreated with 100 nM for 6...

Abstract Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses cause increases in airway epithelial cell mucus electrolyte water secretion into the surface liquid (ASL). Since ASL dehydration inflammation obstruction, ion transporters could play a role pathogenesis of asthma exacerbations. We previously reported that expression anion transporter pendrin is markedly increased response to IL-13. Herein we...

Rationale: Increased production of mucus is a prominent feature asthma. IL-13–driven mucous cell metaplasia associated with decreased expression the transcription factor FOXA2 and increased related FOXA3 in animal culture models.Objectives: Establish how changes contribute to determine whether altered asthma.Methods: Mice expressing Foxa2 transgene airway epithelial cells mice deficient Foxa3 were analyzed after allergen sensitization challenge. Expression FOXA2, FOXA3, MUC5AC, highly...

Fibril formation of amyloid beta peptide (Abeta) is considered to be responsible for the pathology Alzheimer's disease (AD). The Abeta fibril formed by a protein misfolding process in which intermolecular beta-sheet interactions become stabilized abnormally. Thus, develop potential anti-AD drugs, we screened an in-house library find compounds have profile as breaker. We searched breaker approximately 113,000 compounds. From among screening hits, focused on...

3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain elevated under several pathological states including Huntington's disease. In present study, we examined possible toxicity of 3-HK by injection this substance into rat brain. Intrastriatal (50 nmol) induced tissue damage around injected site. Quinolinic acid (QA) at 200 nmol also damage, which was comparable size to that 50 3-HK. Co-administration MK-801 significantly reduced QA-induced lesion, but failed prevent...

Abstract The retina is highly sensitive to oxidative stress because of its high consumption oxygen associated with the phototransductional processes. Recent findings have suggested that involved in pathology age‐related macular degeneration, a progressive degeneration central retina. A well‐known environmental risk factor light exposure, as excessive and continuous exposure can damage photoreceptors. Nuclear factor‐erythroid 2‐related 2 (Nrf2) transcriptional controls antioxidative responses...

Ocular angiogenesis, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration, are closely related to oxidative stress. Many reports have shown that the cellular protective mechanism against stress inflammatory response has nuclear factor-erythroid 2-related factor-2 (Nrf2) activity. The aim this study was investigate effectiveness Nrf2 activation in treating ocular diseases with abnormal vessels.The effects activators, bardoxolone methyl...

Nuclear factor erythroid 2-related 2 (Nrf2) is a redox-sensitive transcription that binds to antioxidant response elements located in the promoter region of genes encoding many enzymes and phase II detoxifying enzymes. Activation Nrf2 pathway seems protective for organs, although well-known activator, bardoxolone methyl, was evaluated clinically treating chronic kidney disease, it found induce adverse events. Many methyl derivatives, mostly derived by chemical modifications, have already...

Rhodopsin Pro347Leu transgenic rabbits were previously generated as models of retinitis pigmentosa (RP). While the mechanism underlying retinal deterioration in these remains unresolved, it is likely that oxidative stress one factors triggering cellular loss. We have recently succeeded obtaining a novel activator (RS9) nuclear factor erythroid 2-related (Nrf2, also known NFE2L2), which regulates antioxidant transcriptional factors. The purpose this study was to investigate whether RS9 delays...

Abstract Nuclear factor erythroid 2-related 2 (Nrf2) is a transcriptional that regulates many antioxidants, and we have recently succeeded in obtaining novel Nrf2 activator, RS9, from microbial transformation. RS9 categorized as triterpenoid, well-known triterpenoids such RTA 402 (bardoxolone methyl) 408 been tested clinical trials. lotion currently being patients at risk for radiation dermatitis. This prompted us to study the profiles of skin. All above increased level an Nrf2-targeted...

CC chemokine receptor 4 (CCR4) is generally recognized as a preferential marker for T helper 2 cells, and we have previously reported morpholine-derivative CCR4 antagonists, RS-1154 RS-1269. Here, investigate the pharmacological profiles of novel pyrimidine-derivative antagonist, 2-{4-[2-(diethylamino)ethoxy]phenyl}-N-(2,4-difluorobenzyl)-5-fluoropyrimidin-4-amine (RS-1748), which showed potency to inhibit bindings [125I]CCL17 [35S]GTPγS human CCR4-expressing Chinese hamster ovary (CHO)...

Neurotrophic effects in vitro have been generally related to promotion of differentiation, maturation and survival, but little is known about the effect on neuronal circuit formation. The organotypic culture system would be an available technique investigate formation cell-cell interactions. As we reported previously, optical recording a useful comprehend activities from multi-points simultaneously. In this study, investigated whether continuous application basic fibroblast growth factor...

To investigate the immunology of host-tumour interaction, critical for development immunotherapy against cancers, by assessing major histocompatibility complex (MHC) class I expression in both benign and malignant prostate disease, relationship between their degree tumour-infiltrating lymphocytes.Direct serial analysis gene tumours is an extremely sensitive powerful tool monitoring immunological changes solid tumours. Most previous protocols rely mainly on patient's peripheral blood but...

Amyloid beta (A beta) is the principal constituent of senile plaques in Alzheimer's disease patients. We investigated whether A and glutamate affect long-term potentiation (LTP) rat hippocampal slices. Pretreatment with 1 microM beta1-42 alone for 3 h slightly inhibited LTP; however, was maintained 60 min. Although impairment not observed by pretreatment 30 h, impaired LTP significantly. These results raise possibility that neurotoxicity exacerbated enhancement susceptibility to excitatory...

Abstract: Progressive deposition of amyloid β peptide in the senile plaques is a principal event neurodegenerative process Alzheimer's disease. Several reports have demonstrated that cytotoxic using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) as an indicator viability cells. With MTT assay, we screened in‐house library to find compounds which suppress β‐induced inhibition reduction. We previously reported 6‐ethyl‐ N , N' ‐bis(3‐hydroxyphenyl)[1,3,5]triazine‐2,4‐diamine...

There is growing evidence that chemokines recruit leukocytes in allergic, inflammatory and immune responses. CC chemokine receptor 4 (CCR4) implicated as a preferential marker for T helper 2 cells, the cells selectively respond to ligand 17 (CCL17) CCL22. We searched compounds having profile CCR4 antagonist from an in-house library have previously reported 3-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}quinazoline-2,4(1H,3H)-dione (named RS-1154) was capable of...