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141.
Zadro I Sepulcri L Lazzer S Fregolent R Zamparo P 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(6):1767-1773
The purpose of this study was to set up a protocol of intermittent exercise to train young basketball players. Twenty-one players were asked to complete (a) an incremental test to determine maximal oxygen uptake (VO2max), the speed at the ventilatory threshold (vthr) and the energy cost of "linear" running (Cr) and (b) an intermittent test composed of 10 shuttle runs of 10-second duration and 30-seconds of recovery (total duration: about 6 minutes). The exercise intensity (the running speed, vi) was set at 130% of vthr. During the intermittent tests, oxygen uptake (VO2) and blood lactate concentration (Lab) were measured. The average pretraining VO2 calculated for a single bout (131 ± 9 ml · min(-1) kg(-1)) was about 2.4 times greater than the subjects' measured VO2max (54.7 ± 4.6 ml · min(-1) · kg(-1)). The net energy cost of running (9.2 ± 0.9 J · m(-1) · kg(-1)) was about 2.4 times higher than that measured at constant "linear" speed (3.9 ± 0.3 J · m(-1) · kg(-1)). The intermittent test was repeated after 7 weeks of training: 9 subjects (control group [CG]) maintained their traditional training schedule, whereas for 12 subjects (experimental group [EG]) part of the training was replaced by intermittent exercise (the same shuttle test as described above). After training, the VO2 measured during the intermittent test was significantly reduced (p < 0.05) in both groups (-10.9% in EG and - 4.6 in CG %), whereas Lab decreased significantly only for EG (-31.5%). These data suggest that this training protocol is effective in reducing lactate accumulation in young basketball players. 相似文献
142.
Daniela Rossi Annamaria Marra Pietro Picconi Massimo Serra Laura Catenacci Milena Sorrenti Erik Laurini Maurizio Fermeglia Sabrina Pricl Stefania Brambilla Nicoletta Almirante Marco Peviani Daniela Curti Simona Collina 《Bioorganic & medicinal chemistry》2013,21(9):2577-2586
Strong pharmacological evidences indicate that σ1 receptors are implicated in the pathophysiology of all major CNS disorders. In the last years our research group has conducted extensive studies aimed at discovering novel σ1 ligands and we recently selected (R/S)-RC-33 as a novel potent and selective σ1 receptor agonist. As continuation of our work in this field, here we report our efforts in the development of this new σ1 receptor agonist. Initially, we investigated the binding of (R) and (S) enantiomers of RC-33 to the σ1 receptor by in silico experiments. The close values of the predicted affinity of (R)-RC-33 and (S)-RC-33 for the protein evidenced the non-stereoselective binding of RC-33 to the σ1 receptor; this, in turn, supported further development and characterization of RC-33 in its racemic form. Subsequently, we set-up a scaled-up, optimized synthesis of (R/S)-RC-33 along with some compound characterization data (e.g., solubility in different media and solid state characterization by thermal analysis techniques). Finally, metabolic studies of RC-33 in different biological matrices (e.g., plasma, blood, and hepatic S9 fraction) of different species (e.g., rat, mouse, dog, and human) were performed. (R/S)-RC-33 is generally stable in all examined biological matrices, with the only exception of rat and human liver S9 fractions in the presence of NADPH. In such conditions, the compound is subjected to a relevant oxidative metabolism, with a degradation of approximately 65% in rat and 69% in human.Taken together, our results demonstrated that (R/S)-RC-33 is a highly potent, selective, metabolically stable σ1 agonist, a promising novel neuroprotective drug candidate. 相似文献
143.
Fabiana Rodrigues Silva Gasparin Fernando Olinto Carreño Juliana Moraes Mewes Eduardo Hideo Gilglioni Clairce Luzia Salgueiro Pagadigorria Maria Raquel Marçal Natali Karina Sayuri Utsunomiya Rodrigo Polimeni Constantin Amanda Tomie Ouchida Carlos Curti Ingrid C. Gaemers Ronald Petrus Johannes Oude Elferink Jorgete Constantin Emy Luiza Ishii-Iwamoto 《生物化学与生物物理学报:疾病的分子基础》2018,1864(7):2495-2509
144.
Crystal structures of glutamate synthase suggested that a conserved glutamyl residue of the synthase domain (E1013 of Synechocystis sp. PCC 6803 ferredoxin-dependent glutamate synthase, FdGltS) may play a key role in activating glutamine binding and hydrolysis and ammonia transfer to the synthase site in this amidotransferase, in response to the ligation and redox state of the synthase site. The E1013D, N, and A, variants of FdGltS were overproduced in Escherichia coli cells, purified, and characterized. The amino acyl substitutions had no effect on the reactivity of the synthase site nor on the interaction with ferredoxin. On the contrary, a dramatic decrease of activity was observed with the D (approximately 100-fold), N and A (approximately 10,000-fold) variants, mainly due to an effect on the maximum velocity of the reaction. The E1013D variant showed coupling between glutamine hydrolysis at the glutaminase site and 2-oxoglutarate-dependent L-glutamate synthesis at the synthase site, but a sigmoid dependence of initial velocity on L-glutamine concentration. The E1013N variant exhibited hyperbolic kinetics, but the velocity of glutamine hydrolysis was twice that of glutamate synthesis from 2-oxoglutarate at the synthase site. These results are consistent with the proposed role of E1013 in signaling the presence of 2-oxoglutarate (and reducing equivalents) at the synthase site to the glutaminase site in order to activate it and to promote ammonia transfer to the synthase site through the ammonia tunnel. The sigmoid dependence of the initial velocity of the glutamate synthase reaction of the E1013D mutant on glutamine concentration provides evidence for a participation of glutamine in the activation of glutamate synthase during the catalytic cycle. 相似文献
145.
Curti C 《Journal of biochemical and molecular toxicology》2007,21(6):382-3; author reply 383
146.
A Aliverti T Lübberstedt G Zanetti R G Herrmann B Curti 《The Journal of biological chemistry》1991,266(27):17760-17763
Two mutants of the spinach ferredoxin-NADP+ reductase (FNR) were constructed, expressed by using a heterologous expression system previously described (Aliverti, A., Jansen, T., Zanetti, G., Ronchi, S., Herrmann, R. G., and Curti, B. (1990) Eur. J. Biochem. 191, 551-555), and purified to homogeneity. The mutant enzymes FNR-Lys116Gln and FNR-Lys244Gln were similar to the wild-type enzyme in the physicochemical properties measured; however, both enzymes showed a lower activity. Steady-state kinetic analyses and NADP+ binding measurements of the mutant proteins have revealed that the Lys116Gln enzyme had a catalytic efficiency (kcat/KmNADPH) 500-fold lower than that of the wild-type enzyme, and its interaction with NADP+ was greatly impaired. The Lys244Gln enzyme instead had almost the same kcat in the ferricyanide reductase reaction as the wild-type enzyme, while higher values of KmNADPH and Kd for NADP+ were observed. Thus, protein engineering has enabled us to define the role of Lys-116 and Lys-244 in ferredoxin-NADP+ reductase; whereas Lys-244 contributes to the stabilization of the Michaelis complex, the Lys-116 side chain plays an important role also in the further steps of the catalytic cycle, because both Km and kcat are highly affected by the mutation. 相似文献
147.
Michele Zanoni Alba Clara Sarti Alice Zamagni Michela Cortesi Sara Pignatta Chiara Arienti Michela Tebaldi Anna Sarnelli Antonino Romeo Daniela Bartolini Luigino Tosatto Elena Adinolfi Anna Tesei Francesco Di Virgilio 《Cell death & disease》2022,13(1)
Glioblastoma (GBM) is the most lethal brain tumor in adults. Radiation, together with temozolomide is the standard treatment, but nevertheless, relapse occurs in nearly all cases. Understanding the mechanisms underlying radiation resistance may help to find more effective therapies. After radiation treatment, ATP is released into the tumor microenvironment where it binds and activates purinergic P2 receptors, mainly of the P2X7 subtype. Two main P2X7 splice variants, P2X7A and P2X7B, are expressed in most cell types, where they associate with distinct biochemical and functional responses. GBM cells widely differ for the level of P2X7 isoform expression and accordingly for sensitivity to stimulation with extracellular ATP (eATP). Irradiation causes a dramatic shift in P2X7 isoform expression, with the P2X7A isoform being down- and the P2X7B isoform up-modulated, as well as extensive cell death and overexpression of stemness and senescence markers. Treatment with P2X7 blockers during the post-irradiation recovery potentiated irradiation-dependent cytotoxicity, suggesting that P2X7B activation by eATP generated a trophic/growth-promoting stimulus. Altogether, these data show that P2X7A and B receptor isoform levels are inversely modulated during the post-irradiation recovery phase in GBM cells.Subject terms: Senescence, CNS cancer 相似文献
148.
M A Vanoni M Pilone Simonetta B Curti A Negri S Ronchi 《European journal of biochemistry》1987,167(2):261-267
The presence of arginine in the active center of D-amino-acid oxidase is well documented although its role has been differently interpreted as being part of the substrate-binding site or the positively charged residue near the N1-C2 = O locus of the flavin coenzyme. To have a better insight into the role of the guanidinium group in D-amino-acid oxidase we have carried out inactivation studies using phenylglyoxal as an arginine-directed reagent. Loss of catalytic activity followed pseudo-first-order kinetics for the apoprotein whereas the holoenzyme showed a biphasic inactivation pattern. Benzoate had no effect on holoenzyme inactivation by phenylglyoxal and the coenzyme analog 8-mercapto-FAD did not provide any additional protection in comparison to the native coenzyme. Spectroscopic experiments indicated that the modified protein is unable to undergo catalysis owing to the loss of coenzyme-binding ability. Analyses of time-dependent activity loss versus arginine modification or [14C]phenylglyoxal incorporation showed the presence of one arginine essential for catalysis. The protection exerted by the coenzyme is consistent with the involvement of an active-site arginine in the correct binding of FAD to the protein moiety. Comparative analyses of CNBr fragments obtained from apoenzyme, holoenzyme and the 8-mercapto derivative of D-amino-acid oxidase after reaction with phenylglyoxal did not provide unequivocal identification of the essential arginine residue within the primary structure of the enzyme. However, they suggest that it might be localized in the N-terminal portion of the polypeptide chain and point to a role of phenylglyoxal-modifiable arginine in binding to the adenylate/pyrophosphate moiety of the flavin coenzyme. 相似文献
149.
150.
Reactivity of D-amino acid oxidase with 1,2-cyclohexanedione: evidence for one arginine in the substrate-binding site 总被引:2,自引:0,他引:2
C Ferti B Curti M P Simonetta S Ronchi M Galliano L Minchiotti 《European journal of biochemistry》1981,119(3):553-557
D-Amino acid oxidase is inactivated by reaction with 1,2-cyclohexanedione in borate buffer at pH 8.8. The reaction follows pseudo-first-order kinetics. The present of benzoate, a substrate-competitive inhibitor of the enzyme, protects substantially against inactivation. Partial reactivation could be obtained by removal of borate and its substitution with phosphate buffer. The reaction of 1,2-cyclohexanedione with the enzyme at different inhibitor concentrations appears to follow a saturation kinetics, indicating the formation of an intermediate complex between enzyme and inhibitor prior to the inactivation process. The partially inactivated enzyme shows the same apparent Km but a decreased V as compared to the native D-amino acid oxidase. Similarly, the inhibited enzyme fails to bind benzoate. Amino acid analysis of the 1,2-cyclohexanedione-treated enzyme at various times of inactivation shows no loss of amino acid residues except for arginines. Analysis of the reaction data by statistical methods indicates that three arginine residues react with the inhibitor at slightly different rates, and that one of them is essential for catalytic activity. The presence of benzoate, while it prevents the loss of activity, reduces by one the number of arginine residues hit by the reagent in the reaction of 1,2-cyclohexanedione with D-amino acid oxidase. 相似文献