The mechanism responsible for the enhanced myocardial susceptibility to ischemic insult in patients with type 2 diabetes is not clear. The present study examines the effect of rosiglitazone treatment on cardiac insulin sensitization and its association with cardioprotection from ischemia/reperfusion injury in an animal model of diabetes. Male Zucker diabetic fatty (ZDF) rats were treated with rosiglitazone (3 mg ⅐ kg ؊1 ⅐ day ؊1 orally) or vehicle for 8 days before undergoing 30 min of coronary artery ligation, followed by reperfusion for 4 h (apoptosis) or 24 h (infarction). Rosiglitazone reduced the blood levels of glucose, triglycerides, and free fatty acids; enhanced cardiac glucose oxidation; and increased Akt phosphorylation (Akt-pS473) 2.1-fold and Akt kinase activity 1.8-fold in the ischemic myocardium. The phosphorylation of two downstream targets of Akt, glycogen synthase kinase-3 and FKHR (forkhead transcription factor), was also enhanced by 2-and 2.9-fold, respectively. In rosiglitazone-treated rats, the number of apoptotic cardiomyocytes and the myocardial infarct size were decreased by 58 and 46%, respectively, and the myocardial contractile dysfunction was improved. Blockade of the insulin-Akt signaling pathway by wortmannin in the 8-day rosiglitazone-treated ZDF rats resulted in a markedly diminished cardioprotective effect of rosiglitazone. In addition, 8-day rosiglitazone treatment in Zucker lean rats or 2-day rosiglitazone treatment in ZDF rats, both of which showed no change in whole-body insulin sensitivity, resulted in a significant reduction in cardiac infarct size, but to a lesser degree when compared with that observed in 8-day rosiglitazone-treated ZDF rats. These results suggest that chronic treatment with rosiglitazone protects the heart against ischemia/reperfusion injury in ZDF rats, and that the enhanced cardiac protection observed after rosiglitazone treatment might be attributable in part to an improvement in cardiac insulin sensitivity. Diabetes 54:554 -562, 2005
Cassia tora is an annual legume and cultivated as a traditional medicinal herb for multiple therapies including regulation of blood pressure and blood lipid. Because of naturally occurring acidic soils in southeastern China, this plant species may possess strategies for tolerance to low pH and aluminum toxicity. In the search for the regulatory basis of biochemical response to Al, cell wall-bound peroxidases, including lignin-generated peroxidases and NADH oxidases, were investigated in the root tips of C. tora. Activities of both types of peroxidases significantly increased with Al concentrations. Analysis with native PAGE also demonstrated the strong induction of cell wall peroxidases by Al. The Al-induced increasing activities of peroxidases were closely correlated with lignin accumulation and H 2O 2 production. The biochemical effect of exogenous nitric oxide (NO) and methyl jasmonic acid (MJ) was examined to investigate signal properties and lignin synthesis under Al stress. Application of MJ at 10 microM promoted root sensitivity to Al by activating apoplastic peroxidase activity and accumulating H 2O 2 and lignin, whereas the opposite action was found for NO. The sensitivity of apoplastic peroxidases under Al stress was associated with the cross-talk of MJ and NO signals. The analysis reveals that the activity of lipoxygenase (an enzyme for MJ biosynthesis), with its transcripts increased in Al-exposed roots, was depressed by NO exposure. The effect of MJ on intracellular NO production was also investigated. It is shown that NO staining with 4,5-diaminofluorescein diacetate fluorescence was intensified by Al but was suppressed by MJ. These results suggest that NO and MJ may interplay in signaling the cell wall peroxidase activity and lignin synthesis in the roots exposed to Al.
We have investigated pancreatic changes associated with hyperinsulinemia and an insulin secretory response to an oral glucose load in a new rat model for obesity. Male Sprague-Dawley pups were reared on a high-carbohydrate (HC) or high-fat (HF) formula by gastrostomy during the suckling period and were weaned onto a stock diet. These animals remained either nutritionally unchallenged or challenged with a high-sucrose diet during the postweaning period. The HC formula-fed animals showed increased insulin concentrations in the plasma and pancreas and also showed impaired insulin secretory response compared with mother-fed control or HF animals in adult life. Immunocytochemical and morphometric studies revealed that hyperinsulinemia in the HC animals during the preweaning period and also in adult life was associated with hypertrophy of beta-cells in the pancreas. The results show that consumption of a HC formula during the suckling period influences pancreatic islet morphology resulting in hyperinsulinemia which eventually leads to the development of obesity later in adult life.
The present study has evaluated effect of fluroxypyr concentrations 0-0.8 mg l(-1) (a widely-used herbicide for controlling annual or perennial weeds growth) on selected metabolic and stress-related parameters in Oryza sativa plants after 6 days of exposure. Increasing concentrations decreased shoot growth and accumulation of chlorophylls but had no effect on root biomass. Increasing doses led also to increase in superoxide radical, hydrogen peroxide and proline accumulation, while malondialdehyde, an indicator of lipid peroxidation, was constitutively elevated. Histochemical staining with nitroblue tetrazolium and 3, 3-diaminobenzidine were positively correlated with the generation of superoxide radical and H(2)O(2). The fluroxypyr-induced oxidative stress triggered significant changes in activities of superoxide dismutase, catalase, ascorbate peroxidase and peroxidase (POD). Activities of the antioxidant enzymes show a general increase at low fluroxypyr concentrations and a decrease at high fluroxypyr levels (except for POD). Analysis of naturing polyacrylamide gel electrophoresis confirmed these results. These data support the observation that fluroxypyr-triggered oxidative stress was responsible for the disturbance of the growth in the rice plants.
CitationTao L. Oxidation of polyunsaturated fatty acids and its impact on food quality and human health. Mini ReviewPage 135 ABSTRACTFor many years, both preclinical and clinical studies have provided evidences to support the beneficial effects of ω-3 Polyunsaturated fatty acids (PUFAs), particularly Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) in the prevention of chronic diseases. However, recently, an increasing number of studies reported adverse or contradictory effects of ω-3 PUFAs on human health. While dose and experimental condition need to be considered when evaluating these effects, oxidation of PUFAs also serves as an important factor contributing to the inconsistent results. In fact, oxidation of PUFAs happens frequently during food processing and storage, cooking and even after food ingestion. The free radicals and metabolites generated from PUFA oxidation may adversely affect food quality and shelf life by producing off-flavors and reducing nutritional values. The impact of PUFA oxidation in human health is more complicated, depending on the concentration of products, disease background and targets. This review will introduce different types of PUFA oxidation, discuss its impact on food quality and human health and provide some thoughts for the future research directions.
An acetone extract of the leaves of Garcinia oblongifolia showed antiviral activity against enterovirus 71 (EV71) using a cytopathic effect inhibition assay. Bioassay-guided fractionation yielded 12 new prenylated benzoylphloroglucinols, oblongifolins J-U (1-12), and five known compounds. The structures of 1-12 were elucidated by spectroscopic analysis including 1D- and 2D-NMR and mass spectrometry methods. The absolute configurations were determined by a combination of a Mosher ester procedure carried out in NMR tubes and ECD calculations. Compared to ribavirin (IC50 253.1 μM), compounds 1, 4, and 13 exhibited significant anti-EV71 activity in vitro, with IC50 values of 31.1, 16.1, and 12.2 μM, respectively. In addition, the selectivity indices of these compounds were 1.5, 2.4, and 3.0 in African green monkey kidney (Vero) cells, respectively.
1 Considerable evidence indicates that calcium plays a critical role in apoptosis. We have previously shown that benidipine, a vasodilatory calcium channel blocker, attenuates postischemia myocardial apoptosis. The present study was designed to determine the mechanisms by which benidipine exerts its antiapoptotic effect. 2 Adult male rats were subjected to 30 min of ischemia followed by 3 h of reperfusion. Rats were randomized to receive either vehicle or benidipine (10 mg kg À1 , i.v.) 10 min before reperfusion. 3 Compared with rats receiving vehicle, those rats treated with benidipine had reduced postischemic myocardial apoptosis as evidenced by decreased TUNEL-positive staining (8.471.2 vs 15.371.3%, Po0.01) and caspase-3 activity (1.9470.25 vs 3.4370.29, Po0.01). 4 Benidipine treatment significantly reduced mitochondrial cytochrome c release and caspase-9 activation, but had no effect on caspase-8 activation, suggesting that benidipine exerts its antiapoptotic effect by inhibiting the mitochondrial-mediated, but not death receptor-mediated, apoptotic pathway. 5 Benidipine treatment not only increased the maximal activity of ERK1/2 at 10 min after reperfusion, but also prolonged the duration of ERK1/2 activation. Benidipine treatment had no significant effect on other apoptotic regulating molecules, such as p38 MAPK. 6 Taken together, our present study demonstrated for the first time the differential regulation of a calcium channel blocker. Benidipine tilted the balance between ERK1/2 and p38 MAPK toward an antiapoptotic state, decreased mitochondrial cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation and postischemic myocardial apoptosis.
Objective: To investigate the expression profile of circular RNAs (circRNAs) and proposed circRNA–microRNA (miRNA) regulatory network in atrial fibrillation (AF). Methods: Atrial tissues from patients with persistent AF with rheumatic heart disease and non-AF myocardium with normal hearts were collected for circRNA differential expression analyses by high-throughput sequencing. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the differentially expressed genes and AF-related pathways. Co-expression networks of circRNA–miRNA were constructed based on the correlation analyses between the differentially expressed RNAs. Quantitative reverse transcription polymerase chain reaction (PCR) was performed to validate the results. Results: A total of 108 circRNAs were found to be differentially expressed in AF. Among them, 51 were up-regulated, and 57 were down-regulated. Dysregulated circRNAs were validated by quantitative real-time PCR. The GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Furthermore, we constructed correlated expression networks between circRNAs and miRNAs. circRNA19591, circRNA19596, and circRNA16175 interacted with 36, 28, and 18 miRNAs, respectively; miR-29b-1-5p and miR-29b-2-5p were related to 12 down-regulated circRNAs, respectively. Conclusion: Our findings provide a novel perspective on circRNAs involved in AF due to rheumatic heart disease and establish the foundation for future research of the potential roles of circRNAs in AF.
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