LY294002 and wortmannin are chemical compounds that act as potent inhibitors of phosphoinositide 3-kinases (PI3Ks). Both them generally used to inhibit cell proliferation cancer treatment by inhibiting the PI3K/protein kinase B (AKT) signaling pathway. In this study, (but not wortmannin) showed an abnormal ability enhance AKT phosphorylation (at Ser472) specifically in gemcitabine (GEM)-resistant pancreatic (PC) lines PK59 KLM1-R. was shown activate accumulate phospho-AKT at intracellular...

Benzodiazepines (BDZs) enhance GABA A receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, role neurosteroids in clinical effects is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, anticonvulsant/anxiolytic that activates CBRs selectively. Midazolam, but not increased neurosteroid levels...

Children with neurofibromatosis type 1 (NF1) are prone to learning and behavioral abnormalities, including problems spatial attention. The molecular etiology for these deficits is unclear, as previous studies have implicated defective dopamine, cyclic adenosine monophosphate (cAMP), Ras homeostasis. Using behavioral, electrophysiological, primary culture, we now demonstrate that reduced dopamine signaling responsible cAMP-dependent defects in neuron function learning. Collectively, results...

Using an antibody against 5α-reduced neurosteroids, predominantly allopregnanolone, we found that immunostaining in the CA1 region of rat hippocampal slices was confined to pyramidal neurons. This neurosteroid staining increased following 15 min administration 60 mm but not 20 ethanol, and enhancement blocked by finasteride dutasteride, selective inhibitors 5α-reductase, a key enzyme required for allopregnanolone synthesis. Consistent with prior report indicating N-methyl-D-aspartate (NMDA)...

Abstract Low‐level activation of N ‐methyl‐ d ‐aspartate receptors (NMDARs) results in a decrease the ability tetanic stimulation to induce long‐term potentiation (LTP). This NMDAR‐mediated LTP inhibition is observed with low micromolar concentrations NMDA or chelation ambient extracellular zinc. In rat hippocampal slices, we examined whether by 1 μM and zinc share common mechanisms. We found that both forms involve nitric oxide (NO) synthase (NOS) calcineurin. Furthermore, are overcome...

Background/Aim: Adrenocortical carcinoma is a very rare tumor characterized by poor prognosis and high mortality. The origin of this primarily the adrenal cortex. 5-year overall survival rate patients with adrenocortical has not improved despite therapeutic advances. Early detection malignancy remains difficult, no standard curative therapy currently exists. Therefore, it important to understand biology carcinoma, identify prognostic biomarkers molecular targets for its therapy. DDX39 an...

Uveal melanoma is one of the most common primary intraocular tumors. It arises from melanocytes in uvea and accounts for 3-5% all melanomas. has a high metastatic potential. About half patients develop distant metastases including liver, median survival time been reported to be 4-5 months. Although treatment uveal evolved enucleation eye-saving local treatment, there no impact on occurrence or overall survival. At least 50% will 3-year rate drops rapidly 13%. Therefore, it important find...

Epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells is related to the pathogenesis of subretinal fibrosis such as that associated with macular degeneration. The role myocardin-related transcription factor A (MRTF-A) EMT RPE and was investigated.The migratory activity human RPE-1 culture evaluated using a scratch assay. subcellular distribution MRTF-A cells, well extent mouse model, were determined by immunofluorescence analysis. Expression α-smooth muscle actin...

We previously found that ethanol has complex effects on hippocampal synaptic plasticity, inhibiting long-term potentiation (LTP) and depression by different mechanisms. The block of appears to be mediated N-methyl-d-aspartate receptors, whereas the LTP involves augmented inhibition via gamma-aminobutyric acid-A receptors (GABA(A)Rs). To pursue factors contributing LTP, we examined ability various concentrations in CA1 region rat slices. Complete required 60 mm ethanol. was enhanced at lower...

Poly (ADP-ribose) polymerase-1 (PARP-1) and autophagy play increasingly important roles in DNA damage repair cell death. Gemcitabine (GEM) remains the first-line chemotherapeutic drug for pancreatic cancer (PC). However, little is known about relationship between PARP-1 expression response to GEM. Here we demonstrate that GEM induces DNA-damage degradation of mono-ADP ribosylated through pathway PC cells, which rescued by inhibiting autophagy. Hypoxia serum starvation inhibit autophagic...

Children with neurofibromatosis type 1 (NF1) frequently have cognitive and behavioral deficits. Some of these deficits been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice). In the current study, we show abnormal motivational influences affect behavior mice, particularly regard to their response novel environmental stimuli. For example, made fewer spontaneous alternations a Y-maze arm entries relative WT controls. However, analysis normalized...

Abstract Epithelial–mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a key role proliferative diseases such as age-related macular degeneration by contributing to subretinal fibrosis. To investigate the potential of retinoic acid receptor-α (RAR-α) signaling this process, we have now examined effects RAR-α agonist Am580 on EMT induced transforming growth factor-β2 (TGF-β2) primary mouse RPE cultured three-dimensional type I collagen gel well fibrosis model. We...

Lactoylglutathione lyase (GLO1), a ubiquitously expressed methylglyoxal (MG) detoxification enzyme, is implicated in the progression of various human malignant diseases. However, role GLO1 development or murine fibrosarcoma still unclear. We performed proteomic analysis to identify differences intracellular proteins regressive tumor cell line QR-32 and inflammatory cell-promoting progressive QRsP-11 by 2DE combined with MS. Seven upregulated were identified compared cells, namely, GLO1,...

We investigated whether artificial aqueous humours are adequate incubation media compared with cerebrospinal fluid (aCSF), and evaluated the retinal toxicity of two vital stains--trypan blue (TB) indocyanine green (ICG)--and triamcinolone acetonide (TA) using isolated rat retinas incubated in humours.In experiment 1, segments were aCSF, BSS plus, Opeguard Neo Kit, or phosphate-buffered saline (PBS). In 2, tissues exposed to one agents plus. Retinal damage was assessed by morphological...

Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment of influenza. Because abnormal behaviors have been observed in some Japanese teenagers following oseltamivir use, its safety has questioned. known to alter neuronal function and behavior animals, particularly when administered combination with ethanol. Based on this, it hypothesized that interactions other drugs may result altered CNS excitability this study. It found injection ephedrine caffeine overcame...

// Yufeng Wang 1 , Yasuhiro Kuramitsu Byron Baron Takao Kitagawa Junko Akada Kazuhiro Tokuda Dan Cui 2 Kazuyuki Nakamura 1, 3 Department of Biochemistry and Functional Proteomics, Yamguchi University Graduate School Medicine, Ube, Japan Pathology, Centre Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan, Correspondence to: Kuramitsu, e-mail: climates@yamaguchi-u.ac.jp Keywords: CGK733, calcium sequestration, PERK/CHOP, ER stress, non-apoptotic death Received: April 02,...