Biomedical subjects

N Gazzah

Publications and source records attributed to N Gazzah.

4 recordsLinked to original sources

PubMed1995

Decrease of brain phospholipid synthesis in free-moving n-3 fatty acid deficient rats.

The autoradiographic method with [14C]-docosahexaenoic acid ([14C]22:6 n-3) was used to determine whether a diet deficient in n-3 fatty acids, inducing a decrease in 22:6 n-3 circulating level, was associated with changes in local rates of phospholipid synthesis in the rat brain. As compared with rats fed a normal diet (peanut plus rapeseed oil), a n-3 fatty acid deficiency [peanut oil group (P group)] induced a generalized decrease (-35 to -76%) of 22:6 n-3 incorporation rates into phospholipids in all the regions examined. This effect was confirmed by using [3H]22:6 n-3 infusion by biochemical analysis and quantifications corrected for the contribution of docosahexaenoate derived from lipid store recycling to the unesterified pool, taken as the precursor pool for phospholipid synthesis in the whole brain. In normal or n-3 fatty acid-deficient rats, the values of the brain-to-plasma 22:6 n-3 specific activity ratio (psi) were similar (0.03), indicating that a considerable endogenous source of 22:6 n-3 (97%), likely derived from phospholipid degradation, dilutes the specific activity of the tracer coming from plasma. Using the specific activity of 22:6 n-3 in plasma instead of brain would thus lead to a gross underestimation of the rate of phospholipid synthesis. The results also demonstrate that the pattern of 14C or 3H distribution in brain lipids was not modified by the n-3 fatty acid-deficient diet. The major lipids labeled were phospholipids, particularly phosphatidylethanolamine. Nevertheless, the unesterified 22:6 n-3 concentrations in plasma and brain were significantly reduced (eight-and threefold, respectively) in the P group. In addition, the proportion of 22:6 n-3 in the brain total lipid fraction, total phospholipids, and phosphatidylcholine, -ethanolamine, and -serine was significantly decreased in n-3 fatty acid-deficient rats. This was partially compensated for by an increase in the 22:5 n-6 level. These results are discussed in relation to the limitation of 22:6 n-3 use to quantify, by the quantitative autoradiographic method, changes in local rates of phospholipid synthesis in rat brain.

Animals↗

PubMed1994

Evidence for brain docosahexaenoate recycling in the free-moving adult rat: implications for measurement of phospholipid synthesis.

The specific activity (SA) of unesterified docosahexaenoic acid (22:6 n-3) in the brain and arterial plasma was measured after constant intravenous infusion of [3H] 22:6 n-3 in the free-moving rat. Within 40-105 min, an apparent steady state of labeled unesterified 22:6 n-3 in plasma and in brain was reached. However, the values of the brain to plasma 22:6 n-3 SA ratios ranged from 0.03 to 0.05, indicating that an isotopic equilibrium between brain and plasma was not attained. This suggests that a considerable endogenous source of unesterified 22:6 n-3 (95-97%) (likely derived from lipid metabolism) dilutes the SA of the tracer coming from plasma. Using the SA of 22:6 in plasma instead of brain would thus lead to a gross underestimation of the rate of phospholipid synthesis.

Animals↗

PubMed1993

Effect of an n-3 fatty acid-deficient diet on the adenosine-dependent melatonin release in cultured rat pineal.

We studied the effect of a diet deficient in n-3 fatty acids on the adenosine-dependent melatonin release from cultured rat pineal gland after stimulation by 5'-N-ethylcarboxamidoadenosine (NECA), an A2 adenosine agonist. Experiments were conducted with 2-month-old rats raised on semipurified diets containing either peanut oil (n-3 deficients) or peanut plus rapeseed oil (controls). The proportion of docosahexaenoic acid (22:6 n-3) in the pineal total lipid fraction and in phosphatidylcholine and phosphatidylethanolamine was significantly decreased in n-3-deficient rats. This was compensated for partially by an increase in 22:4 n-6 and 22:5 n-6 levels. The activity of the cultured rat pineal, in terms of cyclic AMP content and N-acetylserotonin and melatonin release in the medium, was lower after stimulation by 10(-5) mol/L NECA in the group fed peanut oil than in the group fed peanut plus rapeseed oil. The increased ratio of n-6/n-3 fatty acids in pineal total lipids and the major glycerophospholipids (phosphatidylcholine and phosphatidylethanolamine) may have an important influence on the rat pineal responses. The results are discussed in the context of changes in membrane-bound proteins, including enzymes and/or receptors involved in the rat pineal gland function.

Adenosine↗

PubMed1991

Type C Niemann-Pick disease: spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing.

To investigate biochemical heterogeneity within Niemann-Pick type C disease (NPC), the two most characteristic abnormalities, namely (1) kinetics of LDL-stimulated cholesteryl ester formation and (2) intravesicular accumulation of LDL-derived unesterified cholesterol, evaluated by histochemical filipin staining, were studied in cultured skin fibroblasts from a population of 125 NPC patients. Profound alterations (esterification rates less than 10% of normal, very numerous and intensely fluorescent cholesterol-filipin granules) were demonstrated in 86% of the cases, depicting the 'classical' NPC phenotype. The remaining cell lines showed a graded less severe impairment and more transient delay in the induction of LDL-mediated cholesteryl esterification, along with an attenuated accumulation of unesterified cholesterol. In particular, cells from a small group (7%) of patients, which have been individualized as representative of a 'variant' phenotype, showed only slight alterations of esterification, restricted to the early phase of LDL uptake and undistinguishable from those in heterozygotes. In these cells, an abnormal cytochemical distribution of LDL-derived cholesterol, although moderate, was still evident provided rigorous experimental conditions were followed. A third, less clearly individualized group (7%), differing from the classical phenotype mostly by higher rates of cholesteryl ester formation, has been designated as an 'intermediary' phenotype to reflect a more difficult diagnosis of such patients. These findings have an important bearing with regard to diagnosis and genetic counselling, although the significance of such a phenotypic variation in terms of genetic heterogeneity has still to be demonstrated. A given biochemical phenotype was however a constant observation within a family (14 pairs of siblings tested so far). The unique feature of LDL-cholesterol processing alterations in NPC has been further established from comparative studies in Wolman disease and I-cell disease, showing normal or different intracellular distribution of unesterified LDL-derived cholesterol in the latter disorders. Correlation between biochemical and clinical NPC phenotypes was only partial, but a correlation between the severity of alterations in cholesterol processing and sphingomyelin catabolism could be established.

Adolescent↗