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991.
Carvalho C Correia S Santos MS Seiça R Oliveira CR Moreira PI 《Molecular and cellular biochemistry》2008,308(1-2):75-83
Metformin, a drug widely used in the treatment of type 2 diabetes, has recently received attention due to the new and contrasting
findings regarding its effects on mitochondrial function. In the present study, we evaluated the effect of metformin in isolated
rat liver mitochondria status. We observed that metformin concentrations ≥8 mM induce an impairment of the respiratory chain
characterized by a decrease in RCR and state 3 respiration. However, only metformin concentrations ≥10 mM affect the oxidative
phosphorylation system by decreasing the mitochondrial transmembrane potential and increasing the repolarization lag phase.
Moreover, our results show that metformin does not prevent H2O2 production, neither protects against lipid peroxidation induced by the pro-oxidant pair ADP/Fe2+. In addition, we observed that metformin exacerbates Ca2+-induced permeability transition pore opening by decreasing the capacity of mitochondria to accumulate Ca2+ and increasing the oxidation of thiol groups. Taken together, our results show that metformin can promote liver mitochondria
injury predisposing to cell death.
Cristina Carvalho and Sónia Correia contributed equally to this work. 相似文献
992.
The antioxidant activity of β-carotene and oxygenated carotenoids lutein, canthaxanthin, and astaxanthin was investigated
during spontaneous and peroxyl-radical-induced cholesterol oxidation. Cholesterol oxidation, measured as generation of 7-keto-cholesterol
(7-KC), was evaluated in a heterogeneous solution with cholesterol, AAPH, and carotenoids solubilized in tetrahydrofuran and
in water, and in a homogeneous solution of chlorobenzene, with AIBN as a prooxidant. The formation of 7-KC was dependent on
temperature and on cholesterol and prooxidant concentrations. All the carotenoids tested, exhibited significant antioxidant
activity by inhibiting spontaneous, AAPH- and AIBN-induced formation of 7-KC, although the overall order of efficacy of these
compounds was astaxanthin > canthaxanthin > lutein = β-carotene. The finding that carotenoids exert protective effects on
spontaneous and free radical-induced cholesterol oxidation may have important beneficial effects on human health, by limiting
the formation of atheroma and by inhibiting cholesterol oxidation in food processing or storage. 相似文献
993.
de Sales MP Alcazar A Lima LM Amorim TM Pitanga JC Pereira RA Macedo LL Macedo FP Oliveira AS Uchôa AF 《Protein and peptide letters》2008,15(9):1022-1026
The digestive system of P. interpunctella was characterized during its larval development to determination of carbohydrases using disaccharides (sucrose and maltose) and polysaccharides (starch and inulin) as substrate. At 6(th) instar larval, Invertase>alpha-amylase> maltase activities peaks were observed. Invertase was fractionated with acetone and isolated. The Invertase was 485.5 fold purified by Sephacryl S-200 and DEAE-Sephadex. Its kinetic parameters were K(m) of 6.6 mM, V(max) of 0.48, pH optimum of 5.5 and temperature optimum of 30 degrees C. This enzyme was activated by CaCl(2) and inhibited by EDTA. When analyzed by SDS-PAGE it showed one band of M(r) 34 kDa. The understanding of the digestive system of P. interpunctella could be a key step in the design of bioinsecticides. 相似文献
994.
995.
C.R. Vieira M.F. Marques P.R. Soares L. Matuda C.M.A. de Oliveira L. Kato C.C. da Silva L.A. Guillo 《Phytomedicine》2008,15(6-7):528-532
On a preliminary screening, relevant in vitro antiproliferative activity was observed to the crude ethanolic extract of Pterodon pubescens seed oil against the human melanoma cell line SK MEL 37. The diethyl ether fraction from crude ethanolic extract which exhibited stronger activity was submitted to fractionation by gradient elution with hexane/ethyl acetate. Subfraction A, eluted by hexane/ethyl acetate (80:20), was essentially the most active between all the assayed subfractions with an IC50 of 37 μg/ml calculated by the MTT colorimetric method. At this concentration, subfraction A caused morphological features and internucleosomal DNA fragmentation pattern of apoptosis. Through chromatographic separation, the furane diterpene 1 was isolated from this active subfraction and identified by spectral techniques. Compound 1 showed an IC50 value of 32 μM and fluorescence staining with DAPI revealed some typical nuclear changes which are characteristic of apoptosis. These findings support a role for diterpenoids vouacapan-type skeleton as a model to develop new anticancer agents. 相似文献
996.
Shamila S. Gunatilleke Cesar Augusto F. de Oliveira J. Andrew McCammon Amy M. Barrios 《Journal of biological inorganic chemistry》2008,13(4):555-561
Gold(I) compounds have been used in the treatment of rheumatoid arthritis for over 80 years, but the biological targets and
the structure–activity relationships of these drugs are not well understood. Of particular interest is the molecular mechanism
behind the antiarthritic activity of the orally available drug triethylphosphine(2,3,4,6-tetra-O-acetyl-β-1-d-thiopyranosato-S) gold(I) (auranofin, Ridaura). The cathepsin family of lysosomal, cysteine-dependent enzymes is an attractive biological
target of Au(I) and is inhibited by auranofin and auranofin analogs with reasonable potency. Here we employ a combination
of experimental and computational investigations into the effect of changes in the phosphine ligand of auranofin on its in
vitro inhibition of cathepsin B. Sequential replacement of the ethyl substituents of triethylphosphine by phenyl groups leads
to increasing potency in the resultant Au(I) complexes, due in large part to favorable interactions of the more sterically
bulky Au(I)–PR3 fragments with the enzyme active site. 相似文献
997.
Nitric oxide degradation by potato tuber mitochondria: evidence for the involvement of external NAD(P)H dehydrogenases 总被引:1,自引:0,他引:1
The mechanisms of nitric oxide (NO) synthesis in plants have been extensively investigated. NO degradation can be just as important as its synthesis in controlling steady-state levels of NO. Here, we examined NO degradation in mitochondria isolated from potato tubers and the contribution of the respiratory chain to this process. NO degradation was faster in mitochondria energized with NAD(P)H than with succinate or malate. Oxygen consumption and the inner membrane potential were transiently inhibited by NO in NAD(P)H-energized mitochondria, in contrast to the persistent inhibition seen with succinate. NO degradation was abolished by anoxia and superoxide dismutase, which suggested that NO was consumed by its reaction with superoxide anion (O2(-)). Antimycin-A stimulated and myxothiazol prevented NO consumption in succinate- and malate-energized mitochondria. Although favored by antimycin-A, NAD(P)H-mediated NO consumption was not abolished by myxothiazol, indicating that an additional site of O2(-) generation, besides complex III, stimulated NO degradation. Larger amounts of O2(-) were generated in NAD(P)H- compared to succinate- or malate-energized mitochondria. NAD(P)H-mediated NO degradation and O2(-) production were stimulated by free Ca2+ concentration. Together, these results indicate that Ca2+-dependent external NAD(P)H dehydrogenases, in addition to complex III, contribute to O2(-) production that favors NO degradation in potato tuber mitochondria. 相似文献
998.
Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression 总被引:1,自引:0,他引:1
Duarte AI Santos P Oliveira CR Santos MS Rego AC 《Biochimica et biophysica acta》2008,1783(6):994-1002
Previously we demonstrated that insulin protects against neuronal oxidative stress by restoring antioxidants and energy metabolism. In this study, we analysed how insulin influences insulin-(IR) and insulin growth factor-1 receptor (IGF-1R) intracellular signaling pathways after oxidative stress caused by ascorbate/Fe2+ in rat cortical neurons. Insulin prevented oxidative stress-induced decrease in tyrosine phosphorylation of IR and IGF-1R and Akt inactivation. Insulin also decreased the active form of glycogen synthase kinase-3beta (GSK-3beta) upon oxidation. Since phosphatidylinositol 3-kinase (PI-3K)/Akt-mediated inhibition of GSK-3beta may stimulate protein synthesis and decrease apoptosis, we analysed mRNA and protein expression of "candidate" proteins involved in antioxidant defense, glucose metabolism and apoptosis. Insulin prevented oxidative stress-induced increase in glutathione peroxidase-1 and decrease in hexokinase-II expression, supporting previous findings of changes in glutathione redox cycle and glycolysis. Moreover, insulin precluded Bcl-2 decrease and caspase-3 increased expression. Concordantly, insulin abolished caspase-3 activity and DNA fragmentation caused by oxidative stress. Thus, insulin-mediated activation of IR/IGF-1R stimulates PI-3K/Akt and inhibits GSK-3beta signaling pathways, modifying neuronal antioxidant defense-, glucose metabolism- and anti-apoptotic-associated protein synthesis. These and previous data implicate insulin as a promising neuroprotective agent against oxidative stress associated with neurodegenerative diseases. 相似文献
999.
do Nascimento CA Lião LM Kato L da Silva CC Tanaka CM Schuquel IT de Oliveira CM 《Carbohydrate research》2008,343(6):1104-1107
A new tetrahydro beta-carboline alkaloid that has an oligosaccharide unit was isolated from the root extracts of the Palicourea coriacea. The structure was elucidated using spectral methods, including 2D NMR: COSY, HMQC, HMBC and NOESY. 相似文献
1000.
Aceric acid (3-C-carboxy-5-deoxy-alpha-l-xylofuranose) residues are present in pectic polysaccharide rhamnogalacturonan II (RG II) in the form of synthetically challenging 1,2-cis-glycofuranosides. To access synthetic fragments of RG II incorporating aceric acid, a four-step procedure based on C-2 epimerisation of initially prepared 1,2-trans-glycofuranoside was developed. Readily available derivatives of branched-chain l-lyxofuranose bearing a 3-C-vinyl group as a masked 3-C-carboxyl group were investigated as potential precursors of aceric acid units. In the first step of the procedure, installation of a participating group at C-2 of the furanose ring ensured stereocontrol of the O-glycosylation, which was carried out with the thioglycoside of 2-O-acetyl-3,5-di-O-benzyl-3-C-vinyl-L-lyxofuranose. After the glycosylation step, the 2-O-acetyl group was removed, the free 2-OH group was oxidised and the resulting ketone was finally reduced to form the C-3-vinyl-L-xylofuranoside. The use of L-Selectride in the key reduction reaction was essential to achieve the required stereoselectivity to generate 1,2-cis-furanoside. 相似文献