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Journal Article 2014; 35(5): 398-404 PubMed PMID: 25275262 Citation  Keywords:  AMP-Activated Protein Kinases:genetics, Adaptor Proteins, Signal Transducing:genetics, Age of Onset, DEAD-box RNA Helicases:genetics, Early Diagnosis, Gene Regulatory Networks, Genetic Markers, Humans, Membrane Proteins:genetics, Minor Histocompatibility .   

OBJECTIVE: Parkinson disease (PD) is a degenerative disorder of the central nervous system, and in the majority of cases, the causes of PD are unknown. Coupled with impressive advances in statistical tools for analyzing large, complex data sets, well-designed microarray experiments are poised to make a big impact in the field of diseases. So we set the study to identify distinct PD-associated candidates.

METHODS: Candidate genes, with statistical significant changes of expression in PD patients' samples, were extracted from a transcriptome-wide microarray data in 105 individuals, which were downloaded from GEO, NCBI, by using statistical methods; Selected findings were confirmed by principal component analysis (PCA) and functional and pathway enrichment analysis were used to further study about the distinct candidates.

RESULTS: A total of 10 distinctly differentially expressed genes were identified in PD patitents' samples. After PCA confirmation, we specifically pointed out 4 genes (PRKAG2, DLG1, DDX3Y, RPS4Y) as the high confidence distinct candidates in PD. Network and functional categories showed that they were most related to translational elongation(GO:0006414) and participated in mTOR signaling pathway(hsa04150).

CONCLUSION: Among 10 distinct genes which are identified in PD patients' samples, DLG1, XIST, DDX3Y and RPS4Y1 genes can classify samples into different group clearly, and they are regarded as high confidence distinct gene biomarkers of PD. Our results provide a systematic view of the functional alterations of PD that may help to elucidate the mechanisms of PD and lead to improved treatments for PD patients....

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Journal Article 2010; 31(Suppl 2): 84-90 PubMed PMID: 21187824 Citation  Keywords:  Antioxidants:pharmacology, Apoptosis:drug effects, Caspase 3:metabolism, Cell Survival:drug effects, Computer Simulation, Dose-Response Relationship, Drug, Humans, In Vitro Techniques, Male, Neutrophils:cytology, Phosphorylation:drug effects, Protein Kina.   

OBJECTIVE: Pterostilbene, a naturally occurring phenolic derivative, exhibits various pharmacological effects, e.g. anti-cancerous, antioxidant, anti-inflammatory and anti-diabetic. Based on our previous study, we assessed the cellular and molecular effects of pterostilbene on human neutrophils and in cell free systems. Experimental and theoretical molecular descriptors of stilbene derivatives were also determined.

METHODS: We assessed the antioxidant properties of pterostilbene using cell free system and computational methods. The effect of pterostilbene on protein kinase C activation/phosphorylation was detected by special anti-phospho protein kinase C antibodies. Membrane associated changes determining the life span of neutrophils and human recombinant caspase-3 assay were examined.

RESULTS: Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly.

CONCLUSION: Pterostilbene, an analog of resveratrol, was identified as a good natural antioxidant compound. However, reducing the oxidative burst of human neutrophils during their activation in vitro with pterostilbene does not include protein kinase C phosphorylation pathway. Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme activity....

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Journal Article 2010; 31(Suppl 2): 69-72 PubMed PMID: 21187819 Citation  Keywords:  Adult, Carcinogens:pharmacology, Dose-Response Relationship, Drug, Humans, Leuzea, Male, Middle Aged, Neutrophils:drug effects, Oxidative Stress:drug effects, Phosphorylation:drug effects, Plant Extracts:pharmacology, Protein Kinase C:metabolism, Reactive.   

OBJECTIVE: Neutrophil leukocytes and macrophages represent professional phagocytic cells. When appropriately stimulated, they undergo dramatic physiological and biochemical changes resulting in phagocytosis, chemotaxis and degranulation with the activation of reactive oxygen species (ROS) production known as the respiratory burst.

DESIGN: In this study we analysed the effect of a crystalline complex fraction of four N-feruloyl-serotonin isomers isolated from the seeds of Leuzea carthamoides on the mechanism of oxidative burst of human neutrophils in vitro.

RESULTS: N-feruloyl-serotonin (N-f-5HT) inhibited dose-dependently oxidative burst of human whole blood and isolated neutrophils in vitro stimulated with phorbol-myristate-acetate (PMA) as measured by luminol/isoluminol enhanced chemiluminescence.In isolated neutrophils stimulated with PMA, N-f-5HT was effective against extracellular as well as intracellular reactive oxygen species. Western blot analysis documented that N-f-5HT in concentrations of 10 and 100 µM significantly decreased PMA-induced phosphorylation of protein kinase C alpha/beta II.

CONCLUSION: The results suggest that N-f-5HT represents an effective naturally occurring substance with potent effect on the oxidative burst of human neutrophils and could be further investigated for its pharmacological activity against oxidative stress in ischaemia-reperfusion, inflammation and other pathological conditions....

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Journal Article 2007; 28(3): 289-294 PubMed PMID: 17627264 Citation  Keywords:  Animals, Apoptosis, Cell Proliferation, Cells, Cultured, Cyclic AMP-Dependent Protein Kinases:physiology, Estradiol:biosynthesis, Extracellular Signal-Regulated MAP Kinases:physiology, Female, Follicle Stimulating Hormone:pharmacology, Granulosa Cells:phy.   

: The peroxisome proliferator-activated receptors (PPARs), including PPARalpha, PPARbeta/delta, and PPARgamma, are a family of transcription factors belonging to the steroid receptor superfamily. In rat ovary, PPARgamma is mainly expressed in granulosa cells of developing follicles, implying a possible role of PPARgamma in ovarian functions. In the present study, the role of PPARgamma and its gonadotrophic regulation in granulosa cells collected from diethylstilbestrol-treated immature rats were studied. The results showed that PPARgamma could inhibit proliferation and induce apoptosis in primarily cultured granulosa cells. PPARgamma could also stimulate the biosynthesis of estradiol and progesterone after FSH pretreatment, and FSH could regulate the functions of PPARgamma through PKA, ERK1/2, and p38 MAPK signaling pathways. These data suggested that PPARgamma may be involved in follicular atresia and FSH-stimulated steroidogenesis during follicle development....

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