DSpace collection: 2011年台俄有機、藥物與生物化學交流暨藥物化學研討會

Lipoic acid ameliorates arsenic trioxide-induced cytotoxicity, HO-1 expression and oxidative stress in THF-1 cells

Thu, 23 Jun 2011 06:57:48 GMT

title: Lipoic acid ameliorates arsenic trioxide-induced cytotoxicity, HO-1 expression and oxidative stress in THF-1 cells abstract: Inorganic arsenic is a common environmental contaminant; chronic exposure to arsenic can alter the physiology of various key immune cells, particularly macrophages. The aim of this research is to elucidate the key parameters associated with arsenic-induced toxicity and investigate the potential and mechanism of a-lipoic acid (LA), a potent thioreducant, for reducing the toxicity in human promonocyte THP-1 cells. We found that a non-lethal concentration of arsenic trioxide (1 uM) significantly induced the expression of heme oxygenase-1 (HO-1), a response biomarker to arsenic, without stimulating measurable superoxide production. Co-treatment of cells with the HO-1 competitive inhibitor zinc protoporphyrin (Znpp) potentiated arsenic- induced cytotoxicity, indicating that HO-1 confers a cytoprotective effect against arsenic toxicity. In addition, low concentrations of arsenic tnoxide (1 and 2.5 uM) markedly inhibited monocyte-to-macrophage differentiation and expression of macrophage markers. Treatment of cells with LA attenuated ^ arsenic trioxide-induced cytotoxicity and HO-1 over-expression and restored the redox state. In addition, LA neutralized arsenic trioxide-inhibition of monocyte maturation into macrophages ana reversed the expression and activity of scavenger receptors. In conclusion, the cytotoxicity of arsenic trioxide is associated with an imbalance of the cellular redox state, and LA can protect cells from arsenic-induced malfunctions either through its reducing activity, direct interacting with arsenic or stimulating other unidentified signaling pathways.

Four New cis-Clerodane-type Furanoditerpenoids of the Dry Stem of Tinospora crispa

Thu, 23 Jun 2011 06:57:48 GMT

title: Four New cis-Clerodane-type Furanoditerpenoids of the Dry Stem of Tinospora crispa abstract: Tinospora crispa (Lour.) Merr (Menispermaceae) is a folk medicine wildly used in Thailand, Malaysia, Indonesia and China to treat jaundice, rheumatism, urinary disorders, and, especially, diabetes mellitus, and is regarded as one of valuable traditional Chinese medicine in China. Our preliminary bioassay test indicated that the methanol extract of both the stems and leaves of this plant showed a dose-dependent effect to stimulate insulin excretion of β-cells. In the previous study, we found Af-formylnornucidferine and cycloeucalenol showed the stimulation of insulin secretion of b-cells. In addition, borapetosides A and C showed the protective effect on the viability ofβ-cells under the treatment of dexamethasone, a glucocorticoid that promotes cell death. Continuing in the study on this plant, tour new clerodane-type fliranoditerpenoids 1-4, as well as 10 known compounds, were isolated from the methanol extract of the dry stem. Herein, we will report the structure elucidation of these new compounds by ID, and 2D-NMR, and other spectra. The biologic activity of these isolates are under investigation.

Interaction Between Surfactin and U-937 Human Macrophages: Cytotoxicity, Reactive Oxygen Species Content, Mitochondria Membrane Potential, Cell Cycle Profiles, and in vitro Proteolytic Stability

Thu, 23 Jun 2011 06:57:47 GMT

title: Interaction Between Surfactin and U-937 Human Macrophages: Cytotoxicity, Reactive Oxygen Species Content, Mitochondria Membrane Potential, Cell Cycle Profiles, and in vitro Proteolytic Stability abstract: Surfactin is a biosurfactant widely used in biomedical applications; however, information on its biocompatibility and stability in humans is limited. Surfactin is hemolytic, and because it is a peptide, its in vivo proteolytic stability must be validated for use in humans. Similar to particulate foreign bodies, surfactin is captured primarily by the human mononuclear phagocyte system. The interactions between surfactin and macrophages are important because macrophages are central in the host defense system and provide opportunities for evaluating the cytotoxicity of surfactin. Hence, we examined the changes in human macrophages (U-937 cells) after they had been treated with surfactin: their dehydrogenase activity, an indicator 01 cell viability, and their intracellular responses- reactive oxygen species content, mitochondrial membrane potential, and cell cycle profiles- were assessed. The in vitro stability of surfactin was analyzed using MALDI-TOF (matrix-assisted laser desorption and ionization with time-of-flight mass spectrometry. Surfactin had dose-dependent toxic effects on U-937 cell viability and damaged surfactin-treated HeLa (human cervical cancer) and NIH/3T3 (mouse fibroblast) cells. Hydrogen peroxide production in surfactin-treated macrophages was unstable. However, superoxide anion content significantly increased relative to that in untreated control cells over the incubation times (0.5 and 1 h). Mitochondrial membrane potential rose dose-dependently relative to that in untreated control cells, except for significant increases at a dose of 5 uM. Apoptosis developed at higher doses after 4 h of incubation at 10 uM. Surfactin was stable for -24 h of incubation. Our findings may provide a better understanding of the action of surfactin in humans.

Role of Cholesterol in |5-Amyloid Precursor Protein Processing and Oligomerization

Thu, 23 Jun 2011 06:57:46 GMT

title: Role of Cholesterol in |5-Amyloid Precursor Protein Processing and Oligomerization abstract: The relationship between cholesterol and (β-amyloid precursor protein (APP) processing is an attractive mystery in the Alzheimer's disease (AD) field. It has been hypothesized that there is a direct interaction between cholesterol and APP, which can be processed into Aβ in its pathogenic pathway. To assess the importance of APP-cholesterol interaction in regulating APF processing, we generate several cholesterol-binding-deficient mutant APP proteins via introducing single-site mutations in the putative cholesterol recognition amino acid consensus (CRAC) sequence of APR Our preliminary result reveals that smaller portion of APP-S622L, which has a lower binding affinity for cholesterol than APP wild-type, is co-fractionated with lipid raft marker flotillin-1 compared to wild-type. The C99/C83 ratio is also influenced by this S622L mutation. Further study shows these mutations influence the oligomenzation properties 01 AFF as well, lhese data suggest tne interaction between cholesterol and APP could be a driving force for distributing APP into lipid raft, which makes APP more accessible to the pathogenically critical protein BACE1.