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Maximal Velocity (maximal + velocity)

Distribution by Scientific Domains

Life Sciences	64%
Medical Sciences	28%

Selected Abstracts

PRECLINICAL STUDY: Effect of cannabinoids on platelet serotonin uptake

ADDICTION BIOLOGY, Issue 2 2007
Marie Velenovská
ABSTRACT Serotonin is involved in many of the same processes affected by cannabinoids; therefore, we investigated in vitro and in vivo effects of these drugs on the function of serotonin transporter. The effect of ,9 -tetrahydrocannabinol (,9 -THC), endocannabinoid anandamide and synthetic cannabinoid receptor agonist WIN 55,212-2 on platelet serotonin uptake and membrane microviscosity was examined in 19 marijuana smokers and 20 controls. (1) Serotonin uptake was inhibited at higher doses of ,9 -THC (IC50 = 139 µmol/l), anandamide (IC50 = 201 µmol/l) or WIN 55,212-2 (IC50 = 17.4 µmol/l); the inhibition was found non-competitive. ,9 -THC, anandamide and WIN 55,212-2 produced different effects on the membrane microviscosity. (2) Maximal velocity of platelet serotonin uptake was significantly increased in a group of chronic marijuana smokers suffering impairment of cognitive functions when compared with controls. Opposite effect of marijuana smoking on the serotonin uptake efficiency was observed in males beside females. In summary, this study provides evidence that (1) Activity of serotonin transporter is acutely affected by cannabinoids at relatively high drug concentrations; this effect is indirect and can be partially accounted for the changes in the membrane microviscosity. (2) Increase of maximal velocity of the serotonin uptake could be understood as adaptation change in the serotonergic system induced by chronic cannabis use. A hypothesis was supported that lowered serotonin uptake may reflect a gender-related differences in effects of psychoactive cannabinoids. [source]

Influence of Genetically Predisposed Diabetes on Ethanol-Induced Depression of Cardiac Contraction in Adult Rat Ventricular Myocytes

EXPERIMENTAL PHYSIOLOGY, Issue 3 2002
Jun Ren
Diabetes mellitus and alcohol (ethanol) intake are two positively correlated major risk factors for cardiovascular abnormalities. However, the interaction of the two on cardiac function is largely unknown. The purpose of the present study was to examine the impact of genetically predisposed diabetes on acute ethanol exposure-induced cardiac contractile depression at the myocyte level. Ventricular myocytes from spontaneously biobreeding diabetes-prone (BBDP) rats and their diabetes-resistant littermates (BBDR) were stimulated to contract at 0.5 Hz. Contractile properties analysed include: peak shortening amplitude (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (± dL/dt). BBDP rats displayed hyperglycaemia, reduced body weight gain and increased cardiac, hepatic and renal size. Myocytes isolated from BBDP rat hearts exhibited prolonged TPS and TR90 associated with normal PS and ± dL/dt, compared with myocytes from the BBDR group. Acute ethanol exposure (80-640 mg dl,1) caused a concentration-dependent inhibition of PS in both BBDR and BBDP myocytes. However, the degree of inhibition of PS was significantly reduced in BBDP myocytes compared to that of BBDR myocytes. The maximal inhibition was 52.9% and 28.4% in BBDR and BBDP groups, respectively. Ethanol significantly depressed ± dL/dt in both BBDR and BBDP myocytes. In addition, ethanol did not affect TPS or TR90 in either the BBDR or BBDP group. Collectively, these results suggest that the ethanol-induced depression in cardiac myocyte contraction may be ,shadowed' by genetically predisposed diabetes. [source]

Myocardial Performance Index (Tei Index) Does Not Reflect Long-Term Changes in Left Ventricular Function after Acute Myocardial Infarction

ECHOCARDIOGRAPHY, Issue 1 2003
Torstein Hole M.D.
Aims: To evaluate whether changes in myocardial performance index (MPI or Tei index) were related to changes in other Doppler echocardiographic parameters after acute myocardial infarction, or had any independent prognostic impact in a 2-year observational study. Methods and Results: Seventy-one patients with acute myocardial infarction without heart failure were examined at baseline, 3 months, and 2 years. MPI was significantly related to end-diastolic and end-systolic volume indexes, ejection fraction, maximal velocity, and time velocity integral of early mitral filling wave at 3 months and 2 years. MPI did not contribute significantly to the prediction of any changes in the measures of diastolic or systolic function at 3 months or 2 years. Baseline MPI was significantly higher in patients who later developed heart failure(0.55 ± 0.16)than in other patients(0.43 ± 0.13, P = 0.006), but had no independent predictive power for the development of heart failure or death relative to end-systolic volume index and deceleration time of early mitral filling wave. Conclusion: MPI did not accurately reflect changes in Doppler and two-dimensional echocardiographic measures of diastolic or systolic function during a 2-year follow-up after acute myocardial infarction, and did not have any independent prognostic impact. (ECHOCARDIOGRAPHY, Volume 20, January 2003) [source]

PRECLINICAL STUDY: Effect of cannabinoids on platelet serotonin uptake

Plasticity of human skeletal muscle: gene expression to in vivo function

EXPERIMENTAL PHYSIOLOGY, Issue 5 2007
Stephen D. R. Harridge
Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (Vmax), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing Vmax and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level. [source]

Characterization of DNA transport in the thermophilic bacterium Thermus thermophilus HB27

FEBS JOURNAL, Issue 18 2006
Cornelia Schwarzenlander
Horizontal gene transfer has been a major force for genome plasticity over evolutionary history, and is largely responsible for fitness-enhancing traits, including antibiotic resistance and virulence factors. In particular, for adaptation of prokaryotes to extreme environments, lateral gene transfer seems to have played a crucial role. Recently, by performing a genome-wide mutagenesis approach with Thermus thermophilus HB27, we identified the first genes in a thermophilic bacterium for the uptake of free DNA, a process called natural transformation. Here, we present the first data on the biochemistry and bioenergetics of the DNA transport process in this thermophile. We report that linear and circular plasmid DNA are equally well taken up with a high maximal velocity of 1.5 µg DNA·(mg protein),1·min,1, demonstrating an extremely efficient binding and uptake rate of 40 kb·s,1·cell,1. Uncouplers and ATPase inhibitors immediately inhibited DNA uptake, providing clear evidence that DNA translocation in HB27 is an energy-dependent process. DNA uptake studies with genomic DNA of Bacteria, Archaea and Eukarya revealed that Thermus thermophilus HB27 takes up DNA from members of all three domains of life. We propose that the extraordinary broad substrate specificity of the highly efficient Thermus thermophilus HB27 DNA uptake system may contribute significantly to thermoadaptation of Thermus thermophilus HB27 and to interdomain DNA transfer in hot environments. [source]

Anaerobic homolactate fermentation with Saccharomyces cerevisiae results in depletion of ATP and impaired metabolic activity

FEMS YEAST RESEARCH, Issue 3 2009
Derek A. Abbott
Abstract Conversion of glucose to lactic acid is stoichiometrically equivalent to ethanol formation with respect to ATP formation from substrate-level phosphorylation, redox equivalents and product yield. However, anaerobic growth cannot be sustained in homolactate fermenting Saccharomyces cerevisiae. ATP-dependent export of the lactate anion and/or proton, resulting in net zero ATP formation, is suspected as the underlying cause. In an effort to understand the mechanisms behind the decreased lactic acid production rate in anaerobic homolactate cultures of S. cerevisiae, aerobic carbon-limited chemostats were performed and subjected to anaerobic perturbations in the presence of high glucose concentrations. Intracellular measurements of adenosine phosphates confirmed ATP depletion and decreased energy charge immediately upon anaerobicity. Unexpectedly, readily available sources of carbon and energy, trehalose and glycogen, were not activated in homolactate strains as they were in reference strains that produce ethanol. Finally, the anticipated increase in maximal velocity (Vmax) of glycolytic enzymes was not observed in homolactate fermentation suggesting the absence of protein synthesis that may be attributed to decreased energy availability. Essentially, anaerobic homolactate fermentation results in energy depletion, which, in turn, hinders protein synthesis, central carbon metabolism and subsequent energy generation. [source]

Enzymatic properties of phenoloxidase from Pieris rapae (Lepidoptera) larvae

INSECT SCIENCE, Issue 4 2006
CHAO-BIN XUE
Abstract The kinetic parameters of partially purified phenoloxidase (PO, EC. 1.14.18.1) from the 5th instar larvae of Pieris rapae (Lepidoptera) were determined, using L-3, 4-dihydroxyphenylalanine (L-DOPA) as substrate. The optimal pH and temperature of the enzyme for the oxidation of L-DOPA were determined to be at pH 7.0 and at 42°C, respectively. The enzyme was stable between pH 6.5 and 7.4 and at temperatures lower than 37°C. At pH 6.8 and 37°C, the Michaelis constant (Km) and maximal velocity (Vm) of the enzyme for the oxidation of L-DOPA were determined to be 0.80 ,mol/L and 1.84 ,mol/ L/min, respectively. Tetra-hexylresorcinol and 4-dodecylresorcinol effectively inhibited activity of phenoloxidase and this inhibition was reversible and competitive, with the IC50 of 1.50 and 1.12 ,mol/L, respectively. The inhibition constants were estimated to be 0.50 and 0.47 ,mol/L, respectively. [source]

Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification

AGING CELL, Issue 2 2005
Shi-Yan Li
Summary Evidence suggests that aging, per se, is a major risk factor for cardiac dysfunction. Oxidative modification of cardiac proteins by non-enzymatic glycation, i.e. advanced glycation endproducts (AGEs), has been implicated as a causal factor in the aging process. This study was designed to examine the role of aging on cardiomyocyte contractile function, cardiac protein oxidation and oxidative modification. Mechanical properties were evaluated in ventricular myocytes from young (2-month) and aged (24,26-month) mice using a MyoCam® system. The mechanical indices evaluated were peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (± dL/dt). Oxidative stress and protein damage were evaluated by glutathione and glutathione disulfide (GSH/GSSG) ratio and protein carbonyl content, respectively. Activation of NAD(P)H oxidase was determined by immunoblotting. Aged myocytes displayed a larger cell cross-sectional area, prolonged TR90, and normal PS, ± dL/dt and TPS compared with young myocytes. Aged myocytes were less tolerant of high stimulus frequency (from 0.1 to 5 Hz) compared with young myocytes. Oxidative stress and protein oxidative damage were both elevated in the aging group associated with significantly enhanced p47phox but not gp91phox expression. In addition, level of cardiac AGEs was ,2.5-fold higher in aged hearts than young ones determined by AGEs-ELISA. A group of proteins with a molecular range between 50 and 75 kDa with pI of 4,7 was distinctively modified in aged heart using one- or two-dimension SDS gel electrophoresis analysis. These data demonstrate cardiac diastolic dysfunction and reduced stress tolerance in aged cardiac myocytes, which may be associated with enhanced cardiac oxidative damage, level of AGEs and protein modification by AGEs. [source]

Post-translational regulation of EAAT2 function by co-expressed ubiquitin ligase Nedd4-2 is impacted by SGK kinases

JOURNAL OF NEUROCHEMISTRY, Issue 4 2006
Christoph Boehmer
Abstract The human excitatory amino acid transporter (EAAT)2 is the major glutamate carrier in the mammalian CNS. Defective expression of the transporter results in neuroexcitotoxicity that may contribute to neuronal disorders such as amyotrophic lateral sclerosis (ALS). The serum and glucocorticoid inducible kinase (SGK) 1 is expressed in the brain and is known to interact with the ubiquitin ligase Nedd4-2 to modulate membrane transporters and ion channels. The present study aimed to investigate whether SGK isoforms and the related kinase, protein kinase B (PKB), regulate EAAT2. Expression studies in Xenopus oocytes demonstrated that glutamate-induced inward current (IGLU) was stimulated by co-expression of SGK1, SGK2, SGK3 or PKB. IGLU is virtually abolished by Nedd4-2, an effect abrogated by additional co-expression of either kinase. The kinases diminish the effect through Nedd4-2 phosphorylation without altering Nedd4-2 protein abundance. SGKs increase the transporter maximal velocity without significantly affecting substrate affinity. Similar to glutamate-induced currents, [3H] glutamate uptake and cell surface abundance of the transporter were increased by the SGK isoforms and down-regulated by the ubiquitin ligase Nedd4-2. In conclusion, all three SGK isoforms and PKB increase EAAT2 activity and plasma membrane expression and thus, may participate in the regulation of neuroexcitability. [source]

Iso-S -petasin, a hypotensive sesquiterpene from Petasites formosanus, depresses cardiac contraction and intracellular Ca2+ transients in adult rat ventricular myocytes

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2003
Lucy B. Esberg
ABSTRACT Petasites formosanus is an indigenous species of the medicinal plant Petasites which has been used to treat hypertension. Both S -petasin and its isoform iso-S -petasin have been shown to be the effective ingredients in P. formosanus. However, their effect on heart function has not been revealed. This study was to examine the effect of iso-S -petasin on cardiac contractile function at the myocyte level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz under 1.0 mm extracellular Ca2+. Contractile properties were evaluated using an lonOptix MyoCam system including peak shortening (PS), time to PS (TPS), time to 90% re-lengthening (TR90) and maximal velocity of shortening/re-lengthening (±dL/dt). Intracellular Ca2+ properties were assessed by fura-2 and presented as Ca2+ -induced Ca2+ release (CICR) and intracellular Ca2+ decay. Acute application of iso-S -petasin (10,7 to 10,4 M) elicited a concentration-dependent inhibition in PS and CICR, with maximal inhibitions of 51.0% and 31.0%, respectively. iso-S -petasin also induced a concentration-dependent inhibition of ± dL/dt without affecting TPS, TR90, baseline intracellular Ca2+ level or intracellular Ca2+ decay. Elevation of extracellular Ca2+ from 1.0 mm to 2.7 mm significantly antagonized the iso-S -petasin-induced depression in PS and CICR. These results demonstrated a direct depressant action of iso-S -petasin on ventricular contraction, which may work in concert with its antihypertensive action to reduce the cardiac load. The iso-S -petasin-induced decrease in CICR may play a role in its cardiac depressant effect. [source]

Short-Term Acetaldehyde Exposure Depresses Ventricular Myocyte Contraction: Role of Cytochrome P450 Oxidase, Xanthine Oxidase, and Lipid Peroxidation

ALCOHOLISM, Issue 4 2003
Nicholas S. Aberle II
Background: Chronic alcoholism leads to the development of alcoholic cardiomyopathy, manifested as ventricular dilation and impaired ventricular contractility. However, the specific toxic mechanism responsible for alcoholic cardiomyopathy remains unclear. One major candidate toxin is the first metabolic product of ethanol, acetaldehyde (ACA). This study was designed to examine the role of cytochrome P450 oxidase 2E1 (CYP 2E1), xanthine oxidase, and lipid peroxidation in the short-term ACA exposure-induced mechanical defects in adult rat ventricular myocytes. Methods: Mechanical and intracellular Ca2+ properties were evaluated by an IonOptix SoftEdge® system. Lipid peroxidation was assessed with malondialdehyde levels by using high-performance liquid chromatography. Results: Short-term (4- to 6-hr) culture of myocytes with ACA (1,100 ,M) in sealed containers with silicone septum depressed cell-shortening amplitude, maximal velocity of shortening/relengthening, and prolonged duration of relengthening, as well as intracellular Ca2+ clearing without any effect on the duration of shortening and electrically stimulated an intracellular Ca2+ increase. It is interesting to note that the ACA-induced effects on myocyte mechanical properties were abolished with co-treatment of the lipid peroxidation inhibitor butylated hydroxytoluene (20 ,M), the CYP 2E1 inhibitor diallyl sulfide (100 ,M), and the xanthine oxidase inhibitor allopurinol (100 ,M). Short-term incubation of ACA with the myocytes also produced a significant increase of the lipid peroxidation end product malondialdehyde, which may be prevented by butylated hydroxytoluene. Conclusions: Collectively, these data provided evidence that ACA depressed cardiomyocyte mechanical function at micromolar levels, possibly through mechanisms related to CYP oxidase, xanthine oxidase, and lipid peroxidation. [source]

Stimulatory effects of the soy phytoestrogen genistein on noradrenaline transporter and serotonin transporter activity

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 4 2010
Yumiko Toyohira
Abstract We examined the effects of genistein, one of the major soy phytoestrogens, on the activity of noradrenaline transporter (NAT) and serotonin transporter. Treatment with genistein (10,nM,10,,M) for 20,min stimulated [3H]noradrenaline (NA) uptake by SK-N-SH cells. Genistein also stimulated [3H]NA uptake and [3H]serotonin uptake by NAT and serotonin transporter transiently transfected COS-7 cells, respectively. Kinetics analysis of the effect of genistein on NAT activity in NAT-transfected COS-7 cells revealed that genistein significantly increased the maximal velocity of NA transport with little or no change in the affinity. Scatchard analysis of [3H]nisoxetine binding to NAT-transfected COS-7 cells showed that genistein increased the maximal binding without altering the dissociation constant. Although genistein is also known to be an inhibitor of tyrosine kinases, daidzein, another soy phytoestrogen and an inactive genistein analogue against tyrosine kinases, had little effect on [3H]NA uptake by SK-N-SH cells. The stimulatory effects on NAT activity were observed by treatment of tyrphostin 25, an inhibitor of epidermal growth factor receptor tyrosine kinase, whereas orthovanadate, a protein tyrosine phosphatase inhibitor, suppressed [3H]NA uptake by NAT-transfected COS-7 cells. These findings suggest that genistein up-regulates the activity of neuronal monoamine transporters probably through processes involving protein tyrosine phosphorylation. [source]

CREATINE KINASE INHIBITOR IODOACETAMIDE ANTAGONIZES CALCIUM-STIMULATED INOTROPY IN CARDIOMYOCYTES

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2009
Jun Ren
SUMMARY 1Inhibition of creatine kinase is known to suppress cardiac contractile reserve in intact hearts, although the underlying mechanism has not been elucidated. 2The present study was designed to examine whether cardiac depression induced by creatine kinase inhibition was due to action at the level of the essential contractile element, namely cardiomyocytes. Adult rat cardiomyocytes were perfused with the creatine kinase inhibitor iodoacetamide (90 µmol/L) for 90 min. Mechanical and intracellular Ca2+ properties were evaluated using edge-detection and fluorescence microscopy, respectively. Myocytes were superfused with normal (1.3 mmol/L) or high (3.3 mmol/L) extracellular Ca2+ contractile buffer. Mechanical function was examined, including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time to 90% PS (TPS90), time to 90% relengthening (TR90) and integration of shortening/relengthening (normalized to PS). Intracellular Ca2+ transients were evaluated using the following indices: resting and rise of fura-2 fluorescence intensity (,FFI) and intracellular Ca2+ decay time constant. 3The results indicate that elevated extracellular Ca2+ stimulated cardiomyocyte positive inotrope, manifested as increased PS, ±dL/dt, area of shortening, resting FFI and ,FFI associated with a shortened TR90 and intracellular Ca2+ decay time constant. High extracellular Ca2+ did not affect TPS90 and area of relengthening. Iodoacetamide ablated high Ca2+ -induced increases in PS, ±dL/dt, area of shortening, resting FFI, ,FFI and shortened TR90 and intracellular Ca2+ decay time constant. Iodoacetamide itself significantly enhanced the area of relengthening and TR90 without affecting other indices. 4Collectively, these data demonstrate that inhibition of creatine kinase blunts high extracellular Ca2+ -induced increases in cardiomyocyte contractile response (i.e. cardiac contractile reserve). [source]