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Y Giudicelli

Publications and source records attributed to Y Giudicelli.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differential distribution of alpha 2-adrenoceptor subtypes and messenger RNA expression between renal cortex of salt-sensitive and salt-resistant Sabra rats.

OBJECTIVE: To assess whether alterations of alpha 2-adrenoceptor subtypes in distribution and gene expression in the renal cortex could explain the predisposition to salt-sensitivity or salt-resistance in Sabra rats. DESIGN: Studies were performed using plasma membranes and RNA preparations from renal cortex of 8- to 10-week-old Sabra salt-sensitive (SBH) and salt-resistant (SBN) rats on a normal-sodium diet. METHODS: The alpha 2-adrenoceptor subtypes were determined by competition experiments with [3H]-yohimbine or [3H]-RX821002. Their gene expression was studied by RNA-directed complementary DNA synthesis followed by Taq DNA polymerase amplification. RESULTS: Binding studies showed that alpha 2B- and alpha 2A-adrenoceptor subtypes represented in SBN 72 and 28% of the maximal binding capacities of the two radioligands, respectively. In contrast, only the alpha 2B subtype was detected in the SBH rat. However, the use of guanoxabenz disclosed alpha 2B-adrenoceptors in alpha 2B1 and alpha 2B2 subtypes. The densities of those alpha 2B subtypes appeared to be higher in the SBH rat than in the SBN rat. Messenger RNA corresponding to alpha 2A and alpha 2B subtypes were found both in SBH rats and in SBN rats. The expression of the alpha 2B subtype was permanently higher in the SBH rats than in the SBN rats. The expression of the alpha 2A gene in the SBH rats suggests a specific SBH post-transcriptional regulation resulting in the absence of alpha 2A-adrenoceptor. CONCLUSIONS: Differences exist in the renal cortex concerning expression and distribution of alpha 2-adrenoceptor subtypes between SBH and SBN rats. From these differences there might result different alpha 2-adrenoceptor-mediated renal functions in SBH and in SBN rats, which could lead to a predisposition to sensitivity or resistance to a high sodium intake.

Animals↗
PubMed1994

Rat preadipocyte adenylyl cyclase: influence of fat localization and androgenic status.

The influence of androgenic status on basal and stimulated cAMP production, adenylyl cyclase activities and immunoblot quantified GS alpha and Gi alpha 2 subunits of the adenylyl cyclase regulatory proteins were compared in confluent preadipocytes from subcutaneous (SC) and deep-intraabdominal (epididymal) fat deposits. Maximal cAMP response to isoproterenol was lower in SC than in epididymal preadipocytes. After castration, this site-specific difference was suppressed. cAMP response to 2-chloroadenosine, which was identical in the two types of preadipocytes, was decreased by castration in epididymal cells but not in SC cells. The catalytic activity of adenylyl cyclase and its maximal response to GTP were higher in epididymal than in SC preadipocytes. This response to GTP was decreased by castration in epididymal preadipocytes while it remained unchanged in SC preadipocytes. The catalytic activity of adenylyl cyclase was unchanged by androgenic status whatever the cell localization. Levels of GS alpha quantified by immunoblotting were not modified whatever the androgenic status and cell origin. Levels of Gi alpha 2 were not affected by the androgenic status as well, but were lower in SC than in epididymal cells. This study shows that components of the adenylyl cyclase system in preadipocytes are differently regulated by the androgenic status depending on the anatomical origin of the cells.

Adenylyl Cyclases↗
PubMed1994

Influence of ovarian status and regional fat distribution on protein kinase C in rat fat cells.

The effects of ovarian status on insulin- and phorbol 12-myristate 13-acetate (TPA)-stimulated lipogenic responses, phorbol ester-specific binding to protein kinase C (PKC) and immunoblot-quantified beta- and epsilon-PKC isoform levels were compared in female rat fat cells from subcutaneous and deep intra-abdominal (parametrial) fat deposits. In control rats, the cytosolic PKC content per cell was 70% lower in subcutaneous than in parametrial adipocytes. In subcutaneous and parametrial fat cells, the cytosolic PKC contents were reduced by ovariectomy and restored to normal by the administration of ovarian hormones (oestradiol plus progesterone). However, the lipogenic response to TPA was unaltered by ovarian status in both fat deposits, contrasting with the insulin-stimulated lipogenic response. This response increased in parametrial fat cells after ovariectomy and returned to normal after ovarian hormone treatment whereas, in subcutaneous fat cells, the insulin response was either unaltered by ovariectomy or increased by the administration of ovarian hormones. This study shows important site-related differences in fat cell PKC content but also reveals a similar modulation of this PKC by ovarian status, regardless of the anatomical localization of the fat cells. The physiological significance of these findings is discussed.

Adipocytes↗
PubMed1993

Regulation of white adipocyte guanine nucleotide binding proteins Gs alpha and Gi alpha 1-2 by testosterone in vivo: influence of regional fat distribution.

The influence of the androgenic status on the steady-state amounts of Gi alpha 1-2 and Gs alpha subunits was compared in hamster fat cell membranes from the femoral subcutaneous (FSC) and epididymal (EP) adipose tissues, using immunoblotting experiments. In sham-operated hamsters, Gi alpha 1-2 and Gs alpha steady-state amounts found in FSC fat cells were 38% and 40% reduced, respectively, as compared to EP adipocytes. In EP fat cells, castration induced a down-regulation of both Gi alpha 1-2 (-39%) and Gs alpha (-33%), whereas testosterone replacement restored Gs alpha, but not Gi alpha 1-2 levels, to control values. In contrast, these G protein alpha-subunits were insensitive to the androgenic status in FSC fat cells. These data provide the first evidence that the androgenic status can modulate the expression of both the Gi alpha 1-2 and Gs alpha subunits of the fat cell adenylate cyclase regulatory Gi and Gs proteins and that this modulation depends on the anatomical origin of these cells.

Adenylyl Cyclases↗
PubMed1993

Modulation by sex hormones of the membranous transducing system regulating fatty acid mobilization in adipose tissue.

This review summarizes recent animal studies performed to determine the possible role played by sex hormones in the sex- and site-related differences characterizing adipocyte lipolytic activity. In both normal female rats and male hamsters, fat cells from deep intra-abdominal sites elicit higher catecholamine-stimulated lipolytic responses than subcutaneous adipocytes. By using ovariectomized rats, it was found that estradiol 'in vivo', while having no effect in subcutaneous cells, promotes catecholamine-stimulated lipolysis in deep intraabdominal adipocytes by increasing their adenylate cyclase catalytic activity. By using castrated hamsters, it was found that both deep intra-abdominal and subcutaneous fat cell lipolytic activities are equally sensitive to testosterone. In these cells, testosterone treatment promotes not only the beta-adrenergic lipolytic responses by increasing both the adenylate cyclase catalytic activity and the Gs alpha level, but also enhances the alpha 2-adrenergic antilipolytic responses through a transcriptional activation of the alpha 2-adrenoceptor expression. These experiments demonstrate that in some, but not all, white adipocytes the adrenergic signal transducing system regulating lipolysis is a target for sex hormones. This finding may have potential importance in the understanding of the mechanisms underlying the sex-related regional specificities of adipose tissue metabolism and distribution.

Adenylyl Cyclases↗
PubMed1993

Weak resistance to oxidation of native lipoproteins in Wistar rats.

We report an impressive decline in plasma lipid resistance to oxidation during Triton-WR-1339-induced hyperlipidemia in rats. This decline is associated with a modification in the balances between alpha-tocopherol and lipids and alpha-tocopherol and ascorbate. These results are consistent with a weak resistance of accumulated native lipoproteins in plasma to oxidation, during a 6-hour time course, and they suggest a misunderstood role of lipoprotein catabolic enzymes: to improve this characteristic. Conclusively, the results lead us to propound Triton-induced hyperlipidemia as an original model for studying the balance impairment between antioxidants and oxidizable substrates.

Animals↗
PubMed1993

Protein kinase in rat adipocytes: influence of androgenic status and regional fat distribution.

The effects of castration and testosterone treatment on insulin- and phorbol ester (TPA)-stimulated lipogenic responses, phorbol dibutyrate-specific binding to protein kinase C (PKC) in the cytosol and the beta-PKC isoform level quantified by immunoblotting were compared in rat fat cells from femoral subcutaneous (SC) and deep intra-abdominal (epididymal) fat deposits. In control rats, the PKC content was lower in SC than in epididymal fat cells. After castration, the difference in PKC content between SC and epididymal fat cells was reduced and restored by testosterone treatment. However, androgenic status failed to modify the PKC content in SC fat cells. The lipogenic response to insulin was also differently regulated by the androgenic status in the two fat deposits. After castration, the response was increased in SC fat cells, while it was blunted in epididymal fat cells. These effects were corrected by testosterone administration. These results demonstrate that, in white adipocytes, PKC is an additional biological parameter which varies according to the anatomical origin of the fat cells. They also provide evidence that PKC is controlled by androgens in vivo and emphasize the regional site specificity of such a control.

Adipocytes↗
PubMed1992

Hormonal activation of the cGMP-inhibited low-Km cyclic AMP phosphodiesterase of rat adipocytes from different sites: influence of ovariectomy.

Hormonal activation of the cGMP-inhibited low Km cyclic AMP phosphodiesterase isoenzyme (cGI.PDE) by effectors, acting either through the cAMP-independent (insulin) or through cAMP-dependent (isoproterenol, forskolin ACTH and 8Br-cAMP) mechanisms, were compared in parametrial (PM) and femoral subcutaneous (SC) adipocytes from sham-operated (SHAM) and ovariectomized (OVX) rats. In SHAM rats, the basal cGI.PDE activity was 50% higher in PM than in SC adipocytes. In OVX rats, the cGi.PDE activatory responses to all the effectors tested remained unchanged in SC, but were completely suppressed in PM adipocytes. The mechanism underlying these defective cGI.PDE activatory responses to cAMP-dependent effectors observed in PM adipocytes after OVX seems to involve protein kinase A, since a decreased activation of cGI.PDE by protein kinase A was also found in these cells. Treatment of OVX rats with both estradiol and progesterone reversed the defective cAMP-dependent activation of cGI.PDE, but not the refractoriness of this isoenzyme to insulin activation. Taken together with previous observations from this laboratory on the fat cell adenylate cyclase system (Lacasa et al. (1991) Endocrinology 128, 747-753), these results: (a) demonstrate that the influence of the ovarian status on the key enzymes controlling cAMP metabolism in fat cells depends on the anatomical origin of these cells, and; (b) provide a biochemical explanation to the insensitivity of the SC adipocyte lipolytic system to ovarian hormones.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Characteristics of the alpha 2/beta-adrenoceptor-coupled adenylate cyclase system and their relationship with adrenergic responsiveness in hamster fat cells from different anatomical sites.

Various studies have shown that the lipolytic response of white adipocytes to catecholamines was dependent on the anatomical origin of these cells. To provide a biological explanation for this phenomenon, we compared hamster white adipocytes, from femoral subcutaneous and epididymal fat, for their lipolytic activities, cAMP responses and adrenoceptor-coupled adenylate cyclase system. Basal and maximal lipolytic responses to the beta-adrenergic (isoproterenol) and the mixed alpha 2/beta-adrenergic (epinephrine) agonists were lower in femoral subcutaneous cells than in epididymal cells, but the alpha 2-adrenergic antilipolytic response to 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline bi-tartate (UK14304) was slightly greater in femoral subcutaneous fat cells than in epididymal fat cells. Identical results were observed for cAMP responses, except for the alpha 2-adrenergic inhibitory response which was identical in both fat deposits. Adrenoceptors studies revealed higher density of inhibitory alpha 2-adrenoceptors 2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline ([3H]RX821002-binding sites) in femoral subcutaneous fat cells than in epididymal fat cells, but identical density of stimulatory beta-adrenoceptors (125I-cyanopindolol-binding sites) and similar subdivision into beta-adrenoceptor subtypes in both adipose deposits. Finally, the level of the alpha-subunits of the stimulatory and inhibitors guanine-nucleotide-binding regulatory proteins, as well as the adenylate cyclase catalytic activity were 40-50% lower in femoral subcutaneous fat cell membranes than in epididymal fat cell membranes. These results suggest that the differences in cAMP and lipolytic responses to catecholamines between epididymal and femoral subcutaneous adipocytes result at least in part from site-related differences in the adenylate cyclase system rather than in the adrenoceptor status.

Adenylyl Cyclases↗
PubMed1992

[Na+/H+ exchangers, alpha-2-adrenergic receptors, sodium sensitivity and arterial hypertension].

Existing evidences indicate that a crossed regulation between alpha 2-adrenergic receptors and Na+/H+ exchanger(s) exists, that Na decreases the affinity of alpha 2-adrenergic receptors for agonists and antagonists, that intracellular Na+ and H+ ion concentrations regulate Na+/H+ exchanger activity, that intracellular pH controls the affinity of the alpha 2-adrenergic receptors for their agonists and antagonists. Alterations of alpha 2-adrenergic receptor densities and allosteric regulation by sodium have been demonstrated in sodium-dependent hypertension in rats. Increased Na+/H+ exchanger activity has been reported in genetic hypertension. Nevertheless, cosegregation experiments and human genetic polymorphism suggest that the exchanger could not be related to hypertension. We propose the following hypothesis: the increased Na+/H+ exchanger characteristic of hypertension could be secondary to the abnormalities of the alpha 2-adrenergic receptors found in hypertension, probably through the alteration of the sodium allosteric effect on these receptors.

Animals↗
PubMed1991

Differential modulation of the adenylate cyclase/cyclic AMP stimulatory pathway by protein kinase C activation in rat adipose tissue and isolated fat cells. Influence of collagenase digestion.

Exposure of rat epididymal fat pad to phorbol 12-myristate 13-acetate (TPA), an activator of protein kinase C, results in an 85% increase in isoproterenol-stimulated cyclic AMP (cAMP) accumulation, an effect which was antagonized by H7, a protein kinase C inhibitor. This promoting action of TPA appears to be related to (i) an increase in the catalytic activity of adenylate cyclase, (ii) an increase in the maximal response of adenylate cyclase to fluoride and guanylimidodiphosphate (GppNHp) with no change in the EC50 value for GppNHp, and (iii) a reduction of the isoproterenol-stimulated low-Km cAMP phosphodiesterase activity present in the 30,000 g pellet of fat pad homogenates. In contrast with fat pads, exposure of isolated rat fat cells to TPA failed to influence their adenylate cyclase response to GppNHp and their cAMP accumulation and lipolysis. However, the other alterations caused by TPA in fat pads were still observed in fat cells. These results suggest that (i) the major alteration responsible for the promoted isoproterenol-stimulated cAMP response observed in fat pads after exposure to TPA is an increased interaction between the alpha s subunit of Gs and the catalytic site of adenylate cyclase and (ii) this increased interaction is dependent on protein kinase C activation and is abolished by collagenase digestion.

Adenylyl Cyclases↗
PubMed1991

Dietary (n-6) polyunsaturated fatty acids affect beta-adrenergic receptor binding and adenylate cyclase activity in pig adipocyte plasma membrane.

The effect of dietary (n-6) polyunsaturated fatty acids (sunflower oil) on pig adipocyte beta-adrenoreceptor and adenylate cyclase activity was examined. Two adipose sites (subcutaneous and perirenal) were compared. The existence of two affinity classes for beta-adrenoreceptors was evidenced. Adenylate cyclase stimulation by isoproterenol was higher in the perirenal fat than in the subcutaneous fat, in parallel to a higher beta-adrenoreceptor density. When sunflower oil was included in the diet, the adenylate cyclase response to beta-agonists was greater, particularly in perirenal fat, as was the affinity of the adrenoreceptors in their high affinity state. However, the number of beta-adrenoreceptors was lower, suggesting that these are spare receptors. Adenylate cyclase stimulation by 5'-guanylylimidophosphate also revealed site- and diet-specific variations indicating alterations at the Gs-protein level. The adenylate cyclase catalytic activity (reflected by the forskolin-stimulated response) in the control group was higher in the subcutaneous fat than in the perirenal fat. In the sunflower oil-fed pigs, the catalytic activity was greater in the perirenal fat relative to controls, leading to similar values in both adipose tissues of sunflower oil-fed pigs. This indicates that the cyclase catalytic subunit activity also depends on the anatomical site of the fat deposit and is influenced by the diet as well. Correlation between these changes in the adenylate cyclase system are discussed in relationship with alterations in the plasma membrane structure.

Adenylyl Cyclases↗
PubMed1991

Influence of ovariectomy and regional fat distribution on the membranous transducing system controlling lipolysis in rat fat cells.

The mechanism by which sex steroid hormones modulate the lipolytic process in fat cells is still not completely understood, particularly at the level of the membrane. As estrogens seem to have regional influence on adipose tissue, we have compared the effects of long term ovariectomy (3 weeks) on the membranous transducing system controlling lipolysis in two rat fat deposits, the femoral sc and the parametrial adipose tissue. These experiments demonstrate the following. 1) Compared to parametrial adipocytes, sc adipocytes have a reduced cAMP production and a decreased beta-adrenoceptor number associated with a reduced lipolytic activity. 2) In parametrial adipocytes, ovariectomy induces a decrease in cAMP production and in both the beta-agonist-stimulated response and the catalytic activity of adenylate cyclase in association with a decreased lipolysis. In contrast, these parameters are unaltered by ovariectomy in sc adipocytes. This study, which reveals site-related differences in the sensitivity of the fat cell adenylate cyclase system to ovarian status, suggests that these differences may explain some of the sex-related regional specificities of adipose tissue metabolism and distribution.

Adenylyl Cyclases↗
PubMed1990

Correction by dexamethasone treatment of the altered lipolytic cascade induced by adrenalectomy in rat adipocytes.

The ability of glucocorticoid-treatment to reverse the metabolic alterations caused by adrenalectomy in rat adipocytes was studied. Correction of the enhanced adenosine antilipolytic effect and of the defect in lipolysis, cyclic AMP and adenylate cyclase responsiveness to guanine nucleotides were all achieved after a 24 h dexamethasone treatment, whereas correction of the defect in beta-adrenoceptor-density required a 48 h treatment. The latter treatment, however, failed to reverse the defect in both the adenylate cyclase catalytic activity and protein content per fat cell. These different kinetics of restoration indicate that correction by dexamethasone of the defective cyclic AMP and lipolytic responses on one hand and of the guanine nucleotide control of adenylate cyclase on the other one are two related phenomenoms.

4-Chloro-7-nitrobenzofurazan↗
PubMed1990

Evidence that testosterone modulates in vivo the adenylate cyclase activity in fat cells.

In male hamster fat cell membranes, the alpha 2-adrenoreceptor-mediated inhibitory response of adenylate cyclase was almost completely suppressed by castration and was restored to control values after testosterone treatment, whereas the cyclase inhibitory response to nicotinic acid was insensitive to androgenic status. Basal and forskolin-, guanylylimidodiphosphate- and isoproterenol-stimulated cyclase activities were decreased by 30-40% after castration and restored to control values after testosterone treatment. In addition, Mn2+ + forskolin-stimulated activity in the presence or absence of GDP beta S was lower (-30%) after castration and normalized after testosterone treatment. Finally, the effects of testosterone described above were completely abolished when the potent androgen receptor antagonist RU 23908 was administered together with testosterone. These results indicate that both the inhibitory and stimulatory responses of adenylate cyclase are promoted by testosterone through an androgen receptor-dependent mechanism; promotion of the inhibitory response concerns specifically the alpha 2-receptor-mediated pathway, whereas promotion of the stimulatory response appears unspecific and mainly due to increased activity of the cyclase catalytic subunit.

Adenylyl Cyclases↗
PubMed1990

Evidence against the "spare" receptor nature of alpha 2-adrenoceptors in hamster white fat cells.

After having established the alpha 2-adrenoceptor nature of the binding sites specifically labeled by the alpha 2-agonist [3H] UK 14304 in hamster adipocytes, two different approaches have been used to determine whether these alpha 2-adrenoceptors were "spare receptors". The first one, consisted to block irreversibly fractions of the receptor population by various concentrations of the alpha 2-antagonist benextramine and determine the relationship between the residual receptor occupancy by UK 14304 and the corresponding magnitude of the cellular inhibitory cyclic AMP response to the alpha 2-adrenergic component of epinephrine under conditions avoiding cyclic AMP breakdown. The second approach was a detailed comparison between alpha 2-receptor occupancy by [3H] UK 14304 and the cyclic AMP inhibitory dose-response curve to this agonist in cells incubated also under conditions avoiding cyclic AMP breakdown. These two experimental approaches clearly showed that the alpha 2-adrenoceptor of hamster adipocytes are not "spare receptors".

Adipose Tissue↗
PubMed1990

Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans.

Iron catalysis is involved in oxygen-derived free radical generation and subsequent lipid peroxidation, which have been reported to occur during cardiopulmonary bypass in humans. We assessed the effects of the iron chelator deferoxamine on the susceptibility of circulating low density lipoproteins (LDLs) to induced peroxidation in 20 adult patients (10 controls and 10 treated) undergoing cardiopulmonary bypass for coronary or valve procedures. Deferoxamine was given both intravenously (30 mg/kg body wt, starting 30 minutes before bypass and extending for the next 4 hours) and as an additive to the cardioplegic solution (250 mg/l). Blood samples were taken from both atria before and immediately after the end of cardiopulmonary bypass. Plasma lipid peroxidation was assessed by measuring spectrophotometrically the thiobarbituric acid reactive substances (TBARS) content of selectively isolated LDLs after their exposure to a peroxidizing agent. Before cardiopulmonary bypass, the right and left atrial blood values of LDL-TBARS were not significantly different between the two groups. Cardiopulmonary bypass resulted in a lipid peroxidation of significantly greater magnitude in control than in treated patients. Postbypass right atrial values for LDL-TBARS (expressed in mumol/mmol LDL-phospholipids) were 45.7 +/- 17.2 (mean +/- SEM) in control patients and 6.9 +/- 2.9 in treated patients (p less than 0.02), whereas in the left atrial blood, LDL-TBARS yielded values of 62.7 +/- 20.5 and 10.3 +/- 3.9, respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗