References of "Havaux, Xavier"
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See detailHeart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase B), but not SGK3 (serum- and glucocorticoid-induced protein kinase 3).
Mouton, Veronique; Toussaint, Louise ULg; Vertommen, Didier et al

in Biochemical Journal (2010), 431(2), 267-75

On the basis of transfection experiments using a dominant-negative approach, our previous studies suggested that PKB (protein kinase B) was not involved in heart PFK-2 (6-phosphofructo2-kinase) activation ... [more ▼]

On the basis of transfection experiments using a dominant-negative approach, our previous studies suggested that PKB (protein kinase B) was not involved in heart PFK-2 (6-phosphofructo2-kinase) activation by insulin. Therefore we first tested whether SGK3 (serum- and glucocorticoid-induced protein kinase 3) might be involved in this effect. Treatment of recombinant heart PFK-2 with [gamma-32P]ATP and SGK3 in vitro led to PFK-2 activation and phosphorylation at Ser466 and Ser483. However, in HEK-293T cells [HEK (human embryonic kidney)-293 cells expressing the large T-antigen of SV40 (simian virus 40)] co-transfected with SGK3 siRNA (small interfering RNA) and heart PFK-2, insulin-induced heart PFK-2 activation was unaffected. The involvement of PKB in heart PFK-2 activation by insulin was re-evaluated using different models: (i) hearts from transgenic mice with a muscle/heart-specific mutation in the PDK1 (phosphoinositide-dependent protein kinase 1)-substrate-docking site injected with insulin; (ii) hearts from PKBbeta-deficient mice injected with insulin; (iii) freshly isolated rat cardiomyocytes and perfused hearts treated with the selective Akti-1/2 PKB inhibitor prior to insulin treatment; and (iv) HEK-293T cells co-transfected with heart PFK-2, and PKBalpha/beta siRNA or PKBalpha siRNA, incubated with insulin. Together, the results indicated that SGK3 is not required for insulin-induced PFK-2 activation and that this effect is likely mediated by PKBalpha. [less ▲]

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See detailAnti-tumor effect of caveolin gene delivery are mediated through the inhibition of the pro-angiogenic and vasodilatating effect of nitric oxide
Brouet, A.; DeWever, Julie; MARTINIVE, Philippe ULg et al

in FASEB Journal (2005)

In tumors, caveolin-1, the structural protein of caveolae, constitutes a key switch through its function as a tumor suppressor and a promoter of metastases. In endothelial cells (EC), caveolin is also ... [more ▼]

In tumors, caveolin-1, the structural protein of caveolae, constitutes a key switch through its function as a tumor suppressor and a promoter of metastases. In endothelial cells (EC), caveolin is also known to directly interact with the endothelial nitric oxide synthase (eNOS) and thereby to modulate nitric oxide (NO)-mediated processes including vasodilation and angiogenesis. In this study, we examined whether the modulation of the stoichiometry of the caveolin/eNOS complex in EC lining tumor blood vessels could affect the tumor vasculature and consecutively tumor growth. For this purpose, we used cationic lipids, which are delivery systems effective at targeting tumor vs. normal vascular networks. We first documented that in vitro caveolin transfection led to the inhibition of both VEGF-induced EC migration and tube formation on Matrigel. The DNA-lipocomplex was then administered through the tail vein of tumor-bearing mice. The direct interaction between recombinant caveolin and native eNOS was validated in coimmunoprecipitation experiments from tumor extracts. A dramatic tumor growth delay was observed in mice transfected with caveolin- vs. sham-transfected animals. Using laser Doppler imaging and microprobes, we found that in the early time after lipofection (e.g., when macroscopic effects on the integrity of the tumor vasculature were not detectable), caveolin expression impaired NO-dependent tumor blood flow. At later stages post-transfection, a decrease in tumor microvessel density in the central core of caveolin-transfected tumors was also documented. In conclusion, our study reveals that by exploiting the exquisite regulatory interaction between eNOS and caveolin and the propensity of cationic lipids to target EC lining tumor blood vessels, caveolin plasmid delivery appears to be a safe and efficient way to block neoangiogenesis and vascular function in solid tumors, independently of any direct effects on tumor cells. [less ▲]

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See detailEffet du colostrum bovin administré à des porcelets au sevrage sur la morphologie de la paroi intestinale et sur le système immunitaire
Boudry, Christelle ULg; Dalle, Marie-Julie; Halleux, Caroline et al

in 37èmes journées de la recherche porcine (2005, February)

Two groups (A and B) of 6 piglets, weaned at 21 days (D0), received ad libitum the same diet during three weeks. The piglets of group A were not submitted to a colostrum supplementation while those of the ... [more ▼]

Two groups (A and B) of 6 piglets, weaned at 21 days (D0), received ad libitum the same diet during three weeks. The piglets of group A were not submitted to a colostrum supplementation while those of the group B received daily and orally 5 g of bovine colostrum. Each week, piglets were weighed and blood was taken on each one of them. One piglet of each group was sacrified on D0 and the rest of the animals on D21. Mesenteric lymph nodes (ML), iléal Peyer patches (iPP), jejunum and spleen biopsies were taken on each piglet before death. The haematological values and the intestinal histo-morphological data between the two groups were not significantly different, but FACS analyses on the lymphocytes in the biopsies and the determination of stimulation index suggested a significative effect of colostrum on the lymphocytes populations, with, in the ML, an increase of the LB population (14 % vs 28 %, P < 0,05) and, in the iPP, a reduction of the LB's (54,99 % vs 8,44 %, P < 0,01) with an increase of the LT cells (16,87 % vs 72,00 %, P < 0,001). An increase of the lymphocyte stimulation index from piglets receiving colostrum was observed the second day of in vitro stimulation with colostrum. In brief, the answer of the immunity system to bovine colostrum seems to be restricted to the intestinal immunity system and is characterised by an activation, a multiplication and a modification of the lymphocytes ratios. [less ▲]

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See detailCardiomyocyte-restricted overexpression of endothelial nitric oxide synthase (NOS3) attenuates beta-adrenergic stimulation and reinforces vagal inhibition of cardiac contraction.
MASSION, Paul ULg; Dessy, Chantal; Desjardins, Fanny et al

in Circulation (2004), 110(17), 2666-72

BACKGROUND: In the heart, nitric oxide synthases (NOS) modulate cardiac contraction in an isoform-specific manner, which is critically dependent on their cellular and subcellular localization. Defective ... [more ▼]

BACKGROUND: In the heart, nitric oxide synthases (NOS) modulate cardiac contraction in an isoform-specific manner, which is critically dependent on their cellular and subcellular localization. Defective NO production by NOS3 (endothelial NOS [eNOS]) in the failing heart may precipitate cardiac failure, which could be reversed by overexpression of NOS3 in the myocardium. METHODS AND RESULTS: We studied the influence of NOS3 in relation to its subcellular localization on the function of cardiomyocytes isolated from transgenic mice overexpressing NOS3 under the alpha-myosin heavy chain promoter (NOS3-TG). Immunoblot analysis demonstrated moderate (5-fold) NOS3 overexpression in cardiomyocytes from NOS3-TG heterozygotes. Caveolar localization of transgenic eNOS was demonstrated by immunofluorescence, coimmunoprecipitation with caveolin-3, sucrose gradient fractionation, and immunogold staining revealed by electron microscopy. Compared with wild-type littermate, contractility of NOS3-TG cardiomyocytes analyzed by videomicroscopy revealed a lower incidence of spontaneous arrhythmic contractions (n=32, P<0.001); an attenuation of the beta-adrenergic positive inotropic response (isoproterenol, 10(-7) mol/L: 62.1+/-7.8% versus 90.8+/-8.0% of maximum Ca2+ response; n=10 to 17; P<0.05); a potentiation of the muscarinic negative chronotropic response (carbamylcholine, 3.10(-8) mol/L: -63.9+/-14% versus -27.7+/-5.6% of basal rate; n=8 to 10; P<0.05), confirmed by telemetry in vivo; and an attenuation of the accentuated antagonism of beta-adrenergically stimulated contraction (-14.6+/-1.5% versus -3.5+/-1.5; n=7 to 11; P<0.05). Cardiomyocyte NOS inhibition reversed all 4 effects (P<0.05). CONCLUSIONS: Moderate overexpression of NOS3, targeted to caveolae in murine cardiomyocytes, potentiates the postsynaptic muscarinic response and attenuates the effect of high concentrations of catecholamines. Cardiomyocyte NOS3 may represent a promising therapeutic target to restore the sympathovagal balance and protect the heart against arrhythmia. [less ▲]

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