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Biomedical subjects

J L Boucher

Publications and source records attributed to J L Boucher.

10 recordsLinked to original sources

Cytochrome P450 catalyzes the oxidation of N omega-hydroxy-L-arginine by NADPH and O2 to nitric oxide and citrulline.

Rat liver microsomes catalyze the oxidative denitration of N omega-hydroxy-L-arginine (NOHA) by NADPH and O2 with formation of citrulline and nitrogen oxides like NO and NO2-. Besides NO2- and citrulline, whose simultaneous formation is linear for at least 20 min, the formation of NO could be detected under the form of its P450 and P420-Fe(II) complexes by UV-visible and EPR spectroscopy. Classical inhibitors of NO-synthases, like N omega-methyl-and N omega-nitro-arginine, fail to inhibit the microsomal oxidation of NOHA to citrulline and NO2-. On the contrary classical inhibitors of hepatic cytochromes P450 like CO, miconazole, dihydroergotamine and troleandomycin, strongly inhibit this monooxygenase reaction. These results show that the oxygenation of NOHA by NADPH and O2 with formation of citrulline and NO can be efficiently catalyzed by cytochromes P450 (with rates up to 1.5 turnovers per min for the cytochromes of the 3A subfamily).

Animals

Formation of nitric oxide by cytochrome P450-catalyzed oxidation of aromatic amidoximes.

Rat liver microsomes catalyze the oxidation of para-hexyloxy-benzamidoxime 1 to the corresponding arylamide 2 and NO2-, by NADPH and O2. Involvement of cytochromes P450 as catalysts of this reaction was shown by the strong inhibitory effects of CO and miconazole and the spectacular increase of the activity upon treatment of rats with dexamethasone, a specific inducer of cytochromes P450 of the 3A subfamily. Formation of NO during oxidation of 1 was shown by detection of the formation of cytochrome P450- and cytochrome P420-Fe(II)-NO complexes by visible and EPR spectroscopy. The formation of these complexes should be responsible, at least in part, for the fast decrease of the rate of microsomal oxidation of 1 with time. These results suggest that exogenous compounds containing amidine or amidoxime functions could act as precursors of NO in vivo after in situ oxidation by cytochromes P450.

Animals

Formation of nitrogen oxides and citrulline upon oxidation of N omega-hydroxy-L-arginine by hemeproteins.

HRP catalyzes the oxidation of N omega-hydroxy-L-arginine (NOHA) by H2O2 with formation of citrulline and NO2- with initial rates of about 0.7 and 0.2 nmol per nmol HRP per min. In the same manner, cytochromes P450 from rat liver microsomes catalyze the oxidation of NOHA to citrulline and NO2- by cumylhydroperoxide. Inhibitors of these hemeproteins (N3- and CN- for HRP and miconazole for P450) strongly inhibit both citrulline and NO2- formation. Rates of NOHA oxidation by these hemeproteins markedly decrease with time presumably because of their denaturation by nitrogen oxides and of the formation of hemeprotein-iron-NO complexes. These results suggest that NO (and other nitrogen oxides) could be formed from oxidation of NOHA by other enzymes than NO-synthases.

Animals

Knowledge and motor performance.

Traditionally, motor skill acquisition has implied that the performance of a given individual on a particular skill is dependent on the amount of prior practice of that skill. However, concepts such as schema theory, or kinetic formulae, or the strategic allocation of resources imply that, even when practising specific skills, performers gain knowledge about their own motor performance which can be used or applied to related or novel situations. An attempt was made to relate the performance of a complex psychomotor task to differing levels of motor skill expertise or knowledge (athlete and nonathlete). 20 subjects performed (1600 responses) on a novel pursuit or tracking task. Analysis indicated that the athletes performed significantly better. Their main advantage appeared to be more in their ability to control and produce fast, accurate movements than in their decision-making. Accepting Henry and Rogers' 1960 proposition that there is no such thing as a general motor ability or coordination factor does not imply that the only alternative is for all motor skills to be specific. It is argued that the differences in the present study arose from the athletes' greater knowledge (schema, kinetic formulae) related to their understanding of their own motor capabilities.

Adult

Metabolism of lipoxins A4 and B4 and of their all-trans isomers by human leukocytes and rat liver microsomes.

Incubation of lipoxin A4 (LXA4) either with human leukocytes or with rat liver microsomes in the presence of NADPH very selectively led to a more polar metabolite retaining the conjugated tetraenic structure of LXA4. Lipoxin B4 (LXB4) underwent a very similar metabolism into a more polar metabolite, whereas the all-trans isomers of LXA4 and LXB4 were selectively transformed by the same biological systems into metabolites derived from the reduction of one of the double bonds of the conjugated tetraene moiety of the starting compounds. Microsomal metabolism of LXA4 and LXB4 was NADPH-dependent and strongly inhibited by CO and miconazole indicating the involvement of cytochrome P-450 monooxygenase enzymes. Striking similarities between the metabolism of lipoxins and that of leukotriene B4 (LTB4) suggest that LXA4 and LXB4 are mainly hydroxylated, on omega or omega-I position, by human leukocytes and rat and human liver microsomes, whereas their all-trans isomers are mainly reduced into conjugated trienic compounds.

Animals

Sex differences and effects of aging on visuomotor coordination.

The purpose of this study was to examine the effects of aging on men and women in processing information required to reproduce direction and distance on a visuomotor task. Subjects (45 men and 45 women) selected from three age groups (25-34 yr., 45-54 yr., 65-74 yr.) were required to estimate blindly the exact criterion location of a target-point they had identified under one of the following conditions: visual, kinesthetic, and visuokinesthetic. Errors in direction (degrees) and in distance (cm) were recorded. The analysis of the total variability in responding (E) indicated that the women of the 65- to 74-yr. age group were significantly less accurate in estimating distance than were the men of the two older age groups (45 to 54 yr., 65 to 74 yr.) and less accurate than were the women of the 25- to 34-yr. age group. No significant differences in estimating distance were found among the three age groups of men. No significant differences for direction were found between men and women.

Adult

[Spatial representation of a two-dimensional pattern].

The purpose of this study was (a) to determine if vision and kinesthesis contribute differentially to the coding of a specific two-dimensional pattern and (b) to identify the effect of repetition on the spatial representation of this pattern. The reproductions of a specific pattern presented visually were compared with those of a pattern presented kinesthetically. The results showed that vision and kinesthesis had contributed equally to the coding of the directional components of the pattern. However, there was dominance of visual information over kinesthetic information when coding the distance between the intersecting points of the pattern, especially at the beginning of the process. Generally speaking, the visual or kinesthetic repetition, or both, have increased favourably the precision with which a specific pattern was reproduced in distance and direction.

Adolescent

Oxidative metabolism of linoleic acid by human leukocytes.

Upon incubation with human leukocytes, [1-14C] linoleic acid is almost exclusively transformed into 13-hydroxy-9Z, 11E-octadecadienoic acid (13-HODE) if the linoleic acid concentration is lower than 50 microM. Identification of 13-HODE was done by GLC-MS at the level of its methyl ester, trimethylsilyl ether and by comparison with authentic 13-HODE in two different HPLC systems. Analysis of the products by chiral phase HPLC shows that 13(S)-hydroxy-9Z, 11E-octadecadienoic acid is by far the major metabolite formed by human leukocytes. Comparison of reactions performed with intact or lyzed cells suggests that the formation of 13(S)-HODE by human leukocytes occurs in two steps, a dioxygenation catalyzed by a 15-lipoxygenase and a reduction of intermediate 13-HPODE by a glutathione-dependent peroxidase.

Chromatography, High Pressure Liquid

Hydroxylation of leukotriene B4 in leukocytes from various species: identification of a metabolite to authentic 5S,12R,19-trihydroxy-6Z,8E,10E,14Z-eicosatetra enoic acid and relative importance of 19- and 20-hydroxylations.

The major hydroxylated metabolite of leukotriene B4 in rat PMNL was found identical (UV spectrum and retention times in 3 different HPLC systems) to a synthetic compound of known stereochemistry, 19-hydroxy-LTB4. PMNL from various species exhibited 3 different types of behaviour for LTB4 hydroxylation. Human and monkey PMNL showed a high hydroxylating activity and a high regioselectivity with almost exclusive formation of products from 20-hydroxylation. Rat and mini-pig PMNL exhibited a very different regioselectivity with major formation of 19-OH-LTB4 (3:1 ratio). Finally, pig and beef PMNL were found almost devoid of any hydroxylating activity toward LTB4.

Animals