Biomedical subjects

B Yang

Publications and source records attributed to B Yang.

At least 55 records · Page 3Linked to original sources

PubMed2001

Effect of lactate on the synaptic potential, energy metabolism, calcium homeostasis and extracellular glutamate concentration in the dentate gyrus of the hippocampus from guinea-pig.

Towards understanding the role of glycolysis on synaptic function, we examined the effect of lactate on synaptic potential, energy metabolism, Ca(2+) homeostasis and extracellular glutamate in the dentate gyrus of guinea-pig hippocampus. Postsynaptic population spikes were recorded from the granule cell layer of the dentate gyrus in guinea-pig hippocampal slices after replacing glucose with lactate in the perfusion medium. Population spikes were not maintained and spontaneously recovered around 35min after the replacement of glucose with lactate. However, ATP levels of the dentate gyrus remained unchanged while those during the glucose-free condition decreased to 73% of the initial levels at 60min. Intracellular Ca(2+) was measured with the calcium indicator dye fura-2 AM, and the population spike was recorded simultaneously. Ca(2+) levels increased concomitantly with the early decay of synaptic potentials, and recovered partially with the spontaneous recovery of synaptic potentials. The time course of decay of population spikes and the increase of Ca(2+) levels during lactate replacement were similar to those during glucose deprivation. Increase in Ca(2+) levels during lactate replacement was completely blocked by the ryanodine receptor/calcium release channel antagonist dantrolene. Glutamate was released more significantly in the medium during lactate replacement than with normal Ringer solution, and less than that during glucose deprivation. Addition of the N-methyl-D-aspartate blocker, D-(-)-2-amino-5-phosphonovaleric acid, and the L-type calcium channel blocker, nimodipine, but not dantrolene blocked spontaneous recovery of population spikes. The results indicate that lactate can maintain energy levels in hippocampal slices, but cannot maintain ion homeostasis in granule cells of the dentate gyrus. Glycolysis plays an important role in maintaining ion homeostasis, and activation of N-methyl-D-aspartate and L-type calcium channels is necessary for support of synaptic function by lactate utilization.

2-Amino-5-phosphonovalerate↗

PubMed2001

Study of polymorphisms in the CYP2E1 gene in patients with alcoholic pancreatitis.

Cytochrome P450IIEI (CYP2E1) is an ethanol-inducible enzyme. Recently, several novel polymorphisms in the CYP2E1 gene have been identified. A polymorphism at position -35 [G(-35)T] appears to be of functional significance in transcription assays. The aim of this study was to investigate if this and other polymorphisms, at position -1019 [C(-1019)T], 4808 [G(4808)A], and 7668 [T(7668)A] of the CYP2E1 gene are associated with alcoholic pancreatitis. DNA was extracted from peripheral blood of 38 patients with alcoholic chronic pancreatitis (CP), 19 patients with alcoholic acute pancreatitis (AP), 46 alcoholic controls (AC), and 155 normal controls (NC). The polymorphisms were examined by digestion with the corresponding restriction endonucleases following PCR amplification. The results have shown that the frequencies of the rare alleles of these polymorphisms were not significantly different between the CP, AP, and AC groups and NC. Therefore, our study results suggest to us that the polymorphisms investigated in the CYP2E1 gene are unlikely to be involved in the susceptibility and pathogenesis of alcoholic pancreatitis.

Chi-Square Distribution↗

PubMed2001

Differential effects of acute ethanol treatment on cardiac contractile function in young adult and senescent mice.

It is understood that marked biochemical, molecular, and performance alterations occur in cardiovascular tissues related to aging. It is logical, therefore, that differences in the cardiovascular response to ethanol consumption, when comparing younger with older individuals, may exist. We compared the left ventricular function of 6- and 15-month-old (senescent) mice and 16-month-old (senescent) inducible nitric oxide synthase knockout mice (n=7 each) before and subsequent to acute treatment with 60% ethanol (2 g/kg, i.p.). A Millar 1.4 Fr conductance/micromanometer catheter was placed into the left ventricle of the mice for acquisition of pressure-volume loops. Heart contractile functions were significantly decreased in the senescent group, compared with findings in the younger mice. Subsequent to ethanol treatment, the younger mice showed a significant reduction in cardiac function, with a 28% decrease in cardiac index, a 29% decrease in end-systolic elastance, and a 16% decrease in preload recruitable stroke work (P<.01). Conversely, the senescent mice showed significantly increased contractile function, with a 40% increase in end-systolic elastance (P<.01) and a 19% increase in preload recruitable stroke work (P<.05). The myocardial cyclic guanosine monophosphate levels were significantly higher in the older group (P<.002), and subsequent to ethanol treatment, they were decreased by 68.5% (P<.001). Northern blot analysis demonstrated inducible nitric oxide synthase message only in senescent myocardial tissues. Moreover, the cardiac function of senescent inducible nitric oxide synthase knockout mice was comparable with that of young mice, and after ethanol treatment, cardiac function decreased significantly, just as that for young mice did, with a 26% decrease in cardiac index (P<.05) and a 23% decrease in preload recruitable stroke work (P<.01). It was concluded that the differential cardiovascular function and response to acute ethanol

Aging↗

PubMed2001

Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential breast tumor imaging agent.

A novel in vivo imaging agent, 99mTc labeled [(N-[2-((3'-N'-propyl-[3,3,1]aza-bicyclononan-3alpha-yl)(2"-methoxy-5-methyl-phenylcarbamate)(2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato] technetium(V) oxide), [99mTc]2, displaying specific binding towards sigma-2 receptors was prepared and characterized. In vitro binding assays showed that the rhenium surrogate of [99mTc]2, Re-2, displayed excellent binding affinity and selectivity towards sigma-2 receptors (K(i) = 2,723 and 22 nM for sigma-1 and sigma-2 receptor, respectively). Preparation of [99mTc]2 was achieved by heating the S-protected starting material, 1, in the presence of acid, reducing agent (stannous glucoheptonate) and sodium [99mTc]pertechnetate. The lipophilic racemic mixture was successfully prepared in 10 to 50% yield and the radiochemical purity was >98%. Separation of the isomers, peak A and peak B, was successfully achieved by using a chiralpak AD column eluted with an isocratic solvent (n-hexane/isopropanol; 3:1; v/v). The peak A and peak B appear to co-elute with the isomers of the surrogate, Re-2, under the same HPLC condition. Biodistribution studies in tumor bearing mice (mouse mammary adenocarcinoma, cell line 66, which is known to over-express sigma-2 receptors) showed that the racemic [99mTc]2 localized in the tumor. Uptake in the tumor was 2.11, 1.30 and 1.11 %dose/gram at 1, 4 and 8 hr post iv injection, respectively, suggesting good uptake and retention in the tumor cells. The tumor uptake was significantly, but incompletely, blocked (about 25-30% blockage) by co-injection of "cold" (+)pentazocine or haloperidol (1 mg/Kg). A majority of the radioactivity localized in the tumor tissue was extractable (>60%), and the HPLC analysis showed that it is the original compound, racemic [99mTc]2 (>98% pure). The distribution of the purified peak A and peak B was determined in the same tumor bearing mice at 4 hr post iv injection. The tumor uptake was similar for both isomers, but the blood and peripheral tissue content for the isomer in peak B was higher than that for the isomer in peak A. It is evident that the isomer in peak A displayed significantly better tumor/blood and tumor/muscle ratios. The higher rate of in vivo metabolism was also confirmed by the higher thyroid uptake values for the isomer in peak B as compared to peak A. In summary, a 99mTc-labeled sigma receptor imaging agent, [99mTc]2, has demonstrated the feasibility of using a 99mTc-labeled agent for imaging sigma receptor expression in tumor cells. This is the first time a subtype-selective 99mTc-labeled agent for imaging sigma receptor sites is reported.

Adenocarcinoma↗

PubMed2001

Fatty acid composition of lipids in sea buckthorn (Hippophaë rhamnoides L.) berries of different origins.

The oil content and fatty acid composition of berries from two subspecies of sea buckthorn (Hippophaë rhamnoides L.) were investigated. The berries of subsp. rhamnoides contained a higher proportion of oil in seeds (11.3% vs 7.3%, p < 0.01), berries (3.5% vs 2.1%, p < 0.001), and seedless parts (2.8% vs 1.7%, p < 0.01) than the berries of subsp. sinensis. Linoleic (18:2n-6) and alpha-linolenic acids (18:3n-3) comprised about 70% of seed oil fatty acids. Palmitoleic acid (16:1n-7), practically absent in the seed oil, comprised 12.1--39.0% of oil in pulp/peel and 8.9--31.0% of that in the whole berries. More linoleic acid (40.9% vs 39.1%) and less alpha-linolenic acid (26.6% vs 30.6%) was found in the seed oil of subsp. sinensis than in the seed oil of subsp. rhamnoides (p < 0.05). The proportion of palmitoleic acid was higher in the oil of berries of subsp. rhamnoides than the berries of subsp. sinensis (26.0% vs 21.5%, 0.05 < p < 0.1), but was vice versa with alpha-linolenic acid (8.8% vs 11.2%, 0.05 < p < 0.1). The proportions of alpha-linolenic acid correlated inversely with oleic and linoleic acids in the seed oil. In the oil of whole berries, the proportion of palmitoleic acid correlated negatively with the proportions of linoleic and alpha-linolenic acids.

Fatty Acids↗

PubMed2001

Phytosterols in sea buckthorn (Hippophaë rhamnoides L.) berries: identification and effects of different origins and harvesting times.

Sterols in seeds, pulp/peel fractions, and whole berries of sea buckthorn (Hippophaë rhamnoides L.) samples belonging to two major subspecies (sinensis and rhamnoides) from Finland and China were analyzed as TMS derivatives by gas chromatography-mass spectrometry after saponification of the oils. The total sterol contents in the seeds, the fresh pulp/peel, and the whole berries were 1200-1800, 240-400, and 340-520 mg/kg, respectively. The corresponding values in the extracted oils were 12-23, 10-29, and 13-33 g/kg. Sitosterol constituted 57-76 and 61-83%, respectively, of the seed and pulp/peel sterols. The sterol content and composition showed little variation between subspecies and collection sites. Different harvesting dates showed significant effects on the levels of some sterols both in the seeds and in the pulp/peel. The sterol profiles obtained are useful for characterizing sea buckthorn and detecting adulterations of the valuable oils. The information provided by the present investigation is also important for further chemical investigation of sea buckthorn sterols and industrial utilization of the berries as a raw material of functional foods.

Mass Spectrometry↗

PubMed2001

Caspase-3 and apoptosis in experimental chronic renal scarring.

BACKGROUND: Caspase-3 is a member of the caspase enzyme family, having a central role in the execution of apoptosis. However, the significance of Caspase-3 in the inappropriate and excessive apoptosis that contributes to the progression of non-immune-mediated renal scarring has not been established. METHODS: Kidneys from sham-operated and subtotal nephrectomized (SNx) rats were harvested on days 7, 15, 30, 60, 90 and 120 post-surgery. These were analyzed for apoptosis (in situ end labeling of DNA, light and electron microscopy), Caspase-3 activity (fluorometric substrate cleavage assay), protein and mRNA (Western and Northern blotting), as well as distribution (immunohistochemistry), inflammation (ED-1 immunohistochemistry) and fibrosis (Masson's Trichrome staining). RESULTS: Apoptosis, inflammation and fibrosis gradually increased in glomeruli, tubules and interstitium of SNx rats. Caspase-3 was mainly located in damaged tubules, but also was found in some glomerular and interstitial cells. Little or no staining was noted in sham-operated kidneys. In SNx kidneys, Caspase-3 activity was significantly increased from day 30 and peaked on day 120 (2.5-fold). This resulted from increases in the 17 and 24 kD active protein subunits. The 32 kD precursor was increased at all time points (1861% on day 120, P < 0.01). Caspase-3 changes were transcription-dependent with the 2.7 kb caspase-3 mRNA significantly increased at all time points (287% on day 120). Caspase-3 activity was a better predictor of apoptosis (Std beta coefficient = 0.347, P < 0.05) than Caspase-3 proteins or mRNA; however, Caspase-3 at all levels correlated with apoptosis, inflammation and fibrosis (all P < 0.01). CONCLUSIONS: Up-regulation of apoptosis in remnant kidneys is likely to be Caspase-3-dependent as it is associated with increases in Caspase-3 at the activity, protein and mRNA levels. Therefore, Caspase-3 is a potential therapeutic target for the modification of renal cell apoptosis and subsequently renal fibrosis.

Animals↗

PubMed2001

Aldose reductase expression is induced by hyperglycemia in diabetic nephropathy.

BACKGROUND: Despite good metabolic control, many patients with type 1 diabetes still develop nephropathy, implicating a role for genetic factors. Recent studies examining the regulatory region of the aldose reductase (ALR2) gene, the rate-limiting enzyme of the polyol pathway, support its role as a candidate gene for nephropathy. Here we report the quantitation of ALR2, together with sorbitol dehydrogenase mRNA in the peripheral blood mononuclear cells (PBMCs) of type 1 diabetic patients with (N = 29) and without nephropathy (N = 11) following stimulation with high levels of D-glucose. METHODS: PBMCs from patients and normal controls were cultured for five days with phytohemagglutinin in either normoglycemia (11 mmol/L D-glucose) or supplemented with 10 mmol/L D-glucose (moderate hyperglyemia) or 20 mmol/L D-glucose (hyperglycemia). The RNA was extracted and analyzed by ribonuclease protection assay. RESULTS: ALR2 mRNA levels were significantly elevated with increasing D-glucose concentration (normal to hyperglycemic) in those patients with nephropathy (P < 0.0001). In marked contrast, in those without nephropathy and in the normal healthy controls, there was no change in mRNA expression. Furthermore, those patients with nephropathy and the Z-2/X susceptibility genotype had the greatest increase in ALR2 mRNA compared with those with low-risk genotypes (P < 0.007). CONCLUSION: These results show that patients with nephropathy exhibit marked disturbances in the expression of the enzyme components of the polyol pathway. Ultimately this leads to tissue damage and ischemia.

Adult↗

PubMed2001

Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration.

Several aquaporin-type water channels are expressed in mammalian airways and lung: AQP1 in microvascular endothelia, AQP3 in upper airway epithelia, AQP4 in upper and lower airway epithelia, and AQP5 in alveolar epithelia. Novel quantitative methods were developed to compare airway fluid transport-related functions in wild-type mice and knockout mice deficient in these aquaporins. Lower airway humidification, measured from the moisture content of expired air during mechanical ventilation with dry air through a tracheotomy, was 54-56% efficient in wild-type mice, and reduced by only 3-4% in AQP1/AQP5 or AQP3/AQP4 double knockout mice. Upper airway humidification, measured from the moisture gained by dry air passed through the upper airways in mice breathing through a tracheotomy, decreased from 91 to 50% with increasing ventilation from 20 to 220 ml/min, and reduced by 3-5% in AQP3/AQP4 knockout mice. The depth and salt concentration of the airway surface liquid in trachea was measured in vivo using fluorescent probes and confocal and ratio imaging microscopy. Airway surface liquid depth was 45 +/- 5 microm and [Na(+)] was 115 +/- 4 mM in wild-type mice, and not significantly different in AQP3/AQP4 knockout mice. Osmotic water permeability in upper airways, measured by an in vivo instillation/sample method, was reduced by approximately 40% by AQP3/AQP4 deletion. In doing these measurements, we discovered a novel amiloride-sensitive isosmolar fluid absorption process in upper airways (13% in 5 min) that was not affected by aquaporin deletion. These results establish the fluid transporting properties of mouse airways, and indicate that aquaporins play at most a minor role in airway humidification, ASL hydration, and isosmolar fluid absorption.

Adsorption↗

PubMed2001

Association of nitric oxide production and apoptosis in a model of experimental nephropathy.

BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.

Animals↗

PubMed2001

Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells.

CYP2J2 is abundant in human heart and its arachidonic acid metabolites, the epoxyeicosatrienoic acids (EETs), have potent vasodilatory, antiinflammatory and cardioprotective properties. This study was designed to examine the role of CYP2J2 in hypoxia-reoxygenation-induced injury in cultured bovine aortic endothelial cells (BAECs). Early passage BAECs were exposed to 24-h hypoxia followed by 4-h reoxygenation (HR). HR resulted in cell injury, as indicated by significant increases in lactate dehydrogenase (LDH) release and trypan blue stained cells (p < 0.01) and was associated with a decrease in CYP2J2 protein expression. Transfection of BAECs with the CYP2J2 cDNA resulted in increased CYP2J2 expression and arachidonic acid epoxygenase activity, compared with cells transfected with an irrelevant green fluorescent protein (GFP) cDNA. HR induced significant injury in GFP-transfected BAECs, as indicated by increases in LDH release and trypan blue-stained cells (p < 0.01); however, the HR-induced injury was markedly attenuated in CYP2J2-transfected cells (p < 0.01). HR increased cellular 8-iso-prostaglandin F(2alpha) (p < 0.05), and decreased eNOS expression, L-arginine uptake and conversion, and nitrite production (p < 0.01) in GFP-transfected BAECs. CYP2J2 transfection attenuated the HR-induced increase in 8-iso-prostaglandin F(2alpha) (p < 0.05) and decreased the amount of extracellular superoxide detected by cytochrome c reduction under normoxic conditions (p < 0.05) but did not significantly affect HR-induced decreases in eNOS expression, L-arginine uptake and conversion, and nitrite production. Treatment of BAECs with synthetic EETs and/or epoxide hydrolase inhibitors also showed protective effects against HR injury (p < 0.05). These observations suggest: (1) HR results in endothelial injury and decreased CYP2J2 expression; (2) transfection with the CYP2J2 cDNA protects against HR injury; and (3) the cytoprotective effects of CYP2J2 may be mediated, at least in part, by antioxidant effects.

Animals↗

PubMed2001

Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels.

Immunocytochemistry showed expression of aquaporin-1 (AQP1) water channels at sites involved in dietary fat processing, including intrahepatic cholangiocytes, gallbladder, pancreatic microvascular endothelium, and intestinal lacteals. To determine whether AQP1 has a role in dietary fat digestion and/or absorption, mice were placed on a diet that contained 50% fat. Whereas wild-type mice (3-3.5 wk of age, 10-12 g) gained 49 +/- 5% (SE, n = 50) body weight in 8 days, and heterozygous mice gained 46 +/- 4%, AQP1 null mice gained only 4 +/- 3%; weights became similar after return to a 6% fat diet after 6 days. The null mice on a high-fat diet acquired an oily appearance, developed steatorrhea with increased stool triglyceride content, and manifested serum hypotriglyceridemia. Supplementation of the high-fat diet with pancreatic enzymes partially corrected the decreased weight gain in null mice. Absorption of [(14)C]oleic acid from small intestine was not affected by AQP1 deletion, as determined by blood radioactivity after duodenal infusion. Lipase activity in feces and small intestine was remarkably greater in AQP1 null than wild-type mice on low- and high-fat diets. Fluid collections done in older mice (that are less sensitive to a high-fat diet) by ductal cannulation showed threefold increased pancreatic fluid flow in response to secretin/cholecystokinin, but volumes, pH, and amylase activities were affected little by AQP1 deletion, nor were bile flow rates and bile salt concentrations. Together, these results establish a dietary fat misprocessing defect in AQP1 null mice.

Age Factors↗

PubMed2001

Nifedipine modulation of biliary GSH and GSSG/ conjugate efflux in normal and regenerating rat liver.

Canalicular glutathione secretion provides the major driving force for bile acid-independent bile flow (BAIF), although the pathways involved are not established. The hypothesis that GSH efflux proceeds by a route functionally distinct from the high-affinity, low-capacity, mrp2-mediated pathway was tested by using perfused rat liver and three choleretic compounds that modify biliary secretion of GSH (the dihydropyridine nifedipine and organic anion probenecid) or GSSG [sodium nitroprusside (SNP)]. Whereas nifedipine (30 microM) stimulated GSH secretion and blocked SNP-stimulated GSSG efflux and choleresis, SNP (1 mM) was ineffective against nifedipine-stimulated GSH efflux or BAIF, suggesting that most GSSG exits through a GSH-inhibitable path independent of high-affinity GSSG/glutathione conjugate transport. Three observations support this proposal. SNP, but not nifedipine, significantly inhibited bromosulfophthalein (BSP, 1 microM) excretion. Probenecid (1 mM) blocked resting or nifedipine-stimulated GSH secretion but only weakly inhibited BSP excretion. Glutathione, but not BSP, efflux capacity was reduced following partial hepatectomy. We suggest GSH efflux is mediated by a high-capacity organic anion pathway capable of GSSG transport when its high-affinity route is saturated.

Animals↗

PubMed2001

Target cells promote the development and functional maturation of neurons derived from a sympathetic precursor cell line.

The role of target interactions in the development and functional maturation of peripheral neurons was investigated using an immortalized sympathetic precursor cell line. bMAH cells underwent neuronal differentiation in response to neurotrophic factors, but maintained an immature neuronal phenotype characterized by small cell bodies and continued cell division. Co-culture with cardiac myocytes, a target of sympathetic innervation, promoted the appearance of large-diameter postmitotic bMAH neurons. Analysis of bMAH maturation in the presence and absence of co-cultured myocytes indicated that myocyte-derived factors promoted the survival of maturing bMAH neurons prior to their acquisition of nerve growth factor dependence. Myocyte interactions also promoted the functional maturation of bMAH neurons, leading to an increase in the localization of synaptic vesicle proteins into neuritic varicosities and the acquisition of sympathetic-like intrinsic electrical properties. Like primary sympathetic neurons, mature bMAH neurons formed functional connections to cardiac myocytes as measured by evoked postsynaptic responses in connected myocytes. The effects of myocyte co-culture on developing bMAH neurons could be mimicked by myocyte conditioned medium, indicating that cardiac myocytes produce soluble factors that promote the appearance of mature neurons. These experiments indicate that targets of innervation play a role in directing the development and final maturation of peripheral neurons.

Action Potentials↗

PubMed2001

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4(+/-), had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4(+/-) mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also significantly reduced in these mice. In contrast, Syn4(+/-) mice displayed normal insulin-stimulated glucose uptake and metabolism in adipose tissue and liver. Together, these data demonstrate that syntaxin 4 plays a critical physiological role in insulin-stimulated glucose uptake in skeletal muscle. Furthermore, reduction in syntaxin 4 protein levels in this tissue can account for the impairment in whole-body insulin-stimulated glucose metabolism in this animal model.

Adipocytes↗

PubMed2001

Comparison of tumor necrosis factor-alpha effect on the expression of iNOS in macrophage and cardiac myocytes.

Proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), are elevated during cardiopulmonary bypass (CPB), heart failure, and inflammatory cardiac and systemic diseases. Elevated TNF-alpha has been linked to diminished cardiac function, decreased systemic vascular resistance, as well as renal and pulmonary dysfunction. It is understood that myocardial tissues can express TNF-alpha, which results in the induction of inducible nitric oxide synthase (iNOS) leading to a significant decline in cardiac function and other direct effects. The hypothesis of this study was to determine if TNF-alpha would stimulate iNOS and its product nitric oxide (NO) similarly in immortalized macrophage and cardiac myocytes. Cultured macrophages (RAW 264.7) and cardiac myocytes (HL-1) were placed into two treatment groups and a control. The treatments included: (1) TNF-alpha and lipopolysaccharide (LPS); and (2) LPS, TNF-alpha, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) incubated for 8 h. The macrophage expression of iNOS increased by 365% (p < 0.01) and its product, NO, increased proportionally. The expression of iNOS in the cardiac myocyte did not increase with TNF-alpha and LPS. However, with the addition of IFN-alpha and IL-1beta iNOS increased to 140% of control (p < 0.05). Myocyte cGMP and NO did not increase significantly with TNF-alpha treatment. This study suggests that HL-1 myocyte iNOS cannot be induced by TNF-alpha, unlike macrophage iNOS. Furthermore, the resultant cardiac dysfunction, secondary to proinflammatory cytokines effects, is regulated via diverse pathways.

Animals↗

PubMed2001

Relationship of electrochemical oxidation of catechins on their antioxidant activity in microsomal lipid peroxidation.

The oxidation potentials of catechins were measured by employing flow-through column electrolysis. The oxidation potentials of catechins were shown to depend on their structures. At the same time, the antioxidant activity of catechins on NADPH-dependent lipid peroxidation in rat liver microsomes was evaluated. Catechins showed a 50% inhibition of lipid peroxidation in the concentration range of 10-51 microM. Among those studied, galloylated catechins exhibited stronger antioxidant activities than those of nongalloylated catechins. A quantitative relationship has been obtained to describe the antioxidant activity of catechins: log IC50 (microM)= 1.56+2.49E1/2 (V)-0.29 logP (r=0.907), where IC50 represents the concentration for 50% inhibition of lipid peroxidation, E1/2 represents the half-wave potential of the first oxidation wave, and P represents the octanol/water partition coefficient. This relationship suggested two important characteristics determining catechin antioxidant activity, namely the ease of oxidation and the lipophilicity.

Animals↗

PubMed2001

Estimation of the antioxidant activities of flavonoids from their oxidation potentials.

A simple electrochemical method for estimating the antioxidant activity (AA) of flavonoids has been developed. The proposed method is based on a measurement of the half-wave potential (E1/2) of the first oxidation wave of flavonoids by using flow-through column electrolysis. At the same time, the lipid peroxidation (LPO) inhibiting effects of these flavonoids were determined. A quantitative structure-activity relationship was obtained to describe the AA of flavonoids: IC50(microM) = 30.36 + 151.50 E1/2 (V) -12.63 log P (r = 0.852), where IC50 represents the concentration for 50% inhibition of LPO, and P represents the octanol/water partition coefficient. This method is expected to be useful for the quick screening of flavonoid antioxidants, and evaluating the AA of flavonoid-containing foods and medicinal plants.

Animals↗