Phosphodiesterase 4 (PDE4) is a promising target for the treatment of Parkinson's disease (PD). However, the underlying mechanism has not yet been well elucidated. Additionally, most of current PDE4 inhibitors produce severe nausea and vomiting response in patients, which limit their clinical application. FCPR16 is a novel PDE4 inhibitor with little emetic potential. In the present study, the n...

We have used microarray-based methods of global gene expression together with quantitative PCR and Western blot analysis to identify dysregulation of genes and aberrant cellular processes in human fibroblasts and in SH-SY5Y neuroblastoma cells made HPRT-deficient by transduction with a retrovirus stably expressing an shRNA targeted against HPRT. Analysis of the microarray expression data by Gen...

Three-dimensional (3D) cell cultivation is a powerful technique for monitoring and understanding diverse cellular mechanisms in developmental cancer and neuronal biology, tissue engineering, and drug development. 3D systems could relate better to in vivo models than two-dimensional (2D) cultures. Several factors, such as cell type, survival rate, proliferation rate, and gene and protein express...

Dysfunction of D-amino acid oxidase (DAO) and DAO activator (DAOA)/G72 genes have been linked to neuropsychiatric disorders. The glutamate hypothesis of schizophrenia has proposed that increased DAO activity leads to decreased D-serine, which subsequently may lead to N-methyl-D-aspartate (NMDA) receptor hypofunction. It has been shown that DAOA binds to DAO and increases its activity. However, ...

The potential toxicity of nanoparticles, particularly to neurons, is a major concern. In this study, we assessed the cytotoxicity of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye (MNPs@SiO2(RITC)) in HEK293 cells, SH-SY5Y cells, and rat primary cortical and dopaminergic neurons. In cells treated with 1.0 μg/μl MNPs@SiO2(RITC), the expression of several genes rel...

SH-SY5Y human neuroblastoma cells express muscarinic M3 receptors as well as insulin receptors, thus offering the opportunity to investigate possible cross-talk following activation of two distinct intracellular signal transduction pathways that convert the precursor phosphatidylinositol (PI) to its 3' phosphate or its 4' phosphate, respectively. In this study, the effect of carbachol on insuli...

The hypoxia inducible factor-1alpha (HIF1alpha) is a key regulator of oxygen homeostasis, modulating cell survival, and growth in cells exposed to hypoxia. In this study, neuroblastoma (NB) cells SH-SY5Y and SK-N-MC were employed to determine the mechanisms regulating adaptation to hypoxia. NB cells were cultured in a serum-free medium in the presence or absence of CoCl(2) (100 muM, hypoxia mim...

Two human neuroblastoma (NB) cell lines, SH-SY5Y and Kelly, were found to express the gene for erythropoietin (EPO) in an oxygen (O(2))-dependent manner. However, NB cells had maximal production of EPO with lower partial pressure of O(2) values than the well-characterized hepatoma cell line HepG2. This maximal EPO expression was preceded by accumulation of the O(2)-sensitive alpha subunit of th...

Many physiological functions of hydrogen sulfide (H2S) have been reported in mammalian cells over the last 20 years. These physiological effects have been ascertained through in vitro treatment of cells with Na2S or NaHS, both of which are precursors of H2S. Since H2S exists as HS- in a neutral solution, a disulfide compound such as cystine could react with HS- in culture medium as well as in t...

The cytoskeletal protein non-erythroid alpha-spectrin is well documented as an endogenous calpain substrate, especially under pathophysiological conditions. In cell necrosis (e.g. maitotoxin-treated neuroblastoma SH-SY5Y cells), alpha-spectrin breakdown products (SBDPs) of 150 kDa and 145 kDa were produced by cellular calpains. In contrast, in neuronal cells undergoing apoptosis (cerebellar gra...