Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain

1994 ◽  
Vol 267 (5) ◽  
pp. R1273-R1279 ◽  
Author(s):  
F. Thies ◽  
C. Pillon ◽  
P. Moliere ◽  
M. Lagarde ◽  
J. Lecerf

The uptake and metabolism of [3H]docosahexaenoic acid (DHA) esterified at the sn-2 position of lysophosphatidylcholine (lysoPC DHA) and in the unesterified form, both bound to albumin, was studied in 20-day-old rats. LysoPC DHA was preferentially recovered in the brain (4-5% of the injected radioactivity) over the unesterified form of DHA (0.3-0.4%). Conversely, the lysoPC form was taken up less than or at the same extent as the unesterified form by the liver, heart, and kidney. In the brain, DHA was mainly recovered in phosphatidylethanolamine whether the esterified or the unesterified form was used, although DHA from lysoPC was esterified at the same extent in phosphatidylcholine and phosphatidylethanolamine after 2.5 min. The uptake of labeled palmitic, oleic, linoleic, and arachidonic acids, esterified or not in lysophosphatidylcholine, was also studied in brain, liver, heart, and kidney. Only the brain preferentially incorporated unsaturated (but not saturated) lysoPC, with the uptake increasing with the degree of unsaturation of the fatty acid moiety. These results strongly suggest that the young rat brain specifically utilizes albumin-lysoPC-containing polyunsaturated fatty acids.

2018 ◽  
Vol 96 (12) ◽  
pp. 1189-1196 ◽  
Author(s):  
Geetika Garg ◽  
Sandeep Singh ◽  
Abhishek Kumar Singh ◽  
Syed Ibrahim Rizvi

N-acetyl-l-cysteine (NAC) is a precursor of cysteine, which is known to increase the level of glutathione (GSH) in the brain. Several neurodegenerative changes linked to oxidative stress take place in the aging brain. This study aimed to assess the neuroprotective effect of NAC supplementation on age-dependent neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14 days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and catalase, and GSH and total thiol respectively, prooxidants such as protein carbonyl, advanced oxidation protein products, reactive oxygen species, and malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide level, acetylcholinesterase activity, and Na+/K+–ATPase activity were measured and gene expression studies were also performed. The results indicated that NAC augmented the level of enzymatic and nonenzymatic antioxidants with a significant reduction in prooxidant levels in old rats. NAC supplementation also downregulated the expression of inflammatory markers (TNF-α, IL-1β, IL-6) and upregulated the expression of marker genes associated with aging (sirtuin-1) and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin basic protein 2) in old rats. The present findings support a neuroprotective role of NAC which has therapeutic implication in controlling age-related neurological disorders.


1970 ◽  
Vol 117 (2) ◽  
pp. 325-331 ◽  
Author(s):  
H. C. Agrawal ◽  
A. H. Bone ◽  
A. N. Davison

1. Inhibition of the rate of incorporation of [35S]methionine into protein by phenylalanine was more effective in 18-day-old than in 8-day-old or adult rat brain. 2. Among the subcellular fractions incorporation of [35S]methionine into myelin proteins was most inhibited in 18-day-old rat brain. 3. Transport of [35S]methionine and [14C]leucine into the brain acid-soluble pool was significantly decreased in 18-day-old rats by phenylalanine (2mg/g body wt.). The decrease of the two amino acids in the acid-soluble pool equalled the inhibition of their rate of incorporation into the protein. 4. Under identical conditions, entry of [14C]glycine into the brain acid-soluble pool and incorporation into protein and uptake of [14C]acetate into lipid was not affected by phenylalanine. 5. It is proposed that decreased myelin synthesis seen in hyperphenylalaninaemia or phenylketonuria may be due to alteration of the free amino acid pool in the brain during the vulnerable period of brain development. Amyelination may be one of many causes of mental retardation seen in phenylketonuria.


1987 ◽  
Vol 244 (2) ◽  
pp. 325-330 ◽  
Author(s):  
M B Lakher ◽  
R J Wurtman

We examined the formation in vivo of molecular subspecies of brain phosphatidylcholine (PC) via the phospholipid-methylation pathway. [3H]Methionine was infused into a lateral cerebral ventricle, and 3H-labelled PC was isolated from brains of rats 0.1-18 h after the infusions. Three major subspecies of this PC, differing in their fatty acid compositions, were separated on silver-impregnated t.l.c. plates, and the proportions of radioactivities in these three PC fractions were determined. The results indicate that newly-formed PC synthesized by methylation of phosphatidylethanolamine at 0.1 h after [3H]methionine contains a significantly higher proportion of polyunsaturated subspecies (i.e. those with six or four double bonds) than does PC obtained later times after injection of [3H]methionine. This change in the composition of 3H-labelled brain PC occurs gradually and is not due to an influx of radioactive PC from the periphery. Our data suggest that polyunsaturated PC (hexaenes and tetraenes) produced in the brain by methylation of phosphatidylethanolamine turns over faster than does that containing more-saturated fatty acids.


1988 ◽  
Vol 255 (2) ◽  
pp. C133-C139 ◽  
Author(s):  
J. T. Tildon ◽  
L. M. Roeder

Recent studies suggest that the utilization of oxidizable substrates by the brain may be regulated in part by transport across the plasma membrane. Dissociated brain cells obtained by mechanical disruption of rat brain were used to measure the uptake of 3-hydroxy[3-14C]butyrate. Total uptake revealed two mechanisms (diffusion and a carrier-mediated system). A Lineweaver-Burk plot of the latter component yielded an apparent Km of 1.47 mM and a maximal velocity (Vmax) of 5 nmol.min-1.mg protein-1. The rates of uptake were temperature dependent and were significantly higher at pH 6.2 than at pH 7.4 or 8.2. Preloading the cells and increasing the intracellular concentration of 3-hydroxybutyrate using 12.5 and 25 mM increased the rate of uptake 143 and 206%, respectively, indicative of an accelerative exchange mechanism. Uptake was inhibited approximately 50% by (in mM) 10 phenylpyruvate, 10 alpha-ketoisocaproate, 10 KCN, and 1.5 NaAsO2. Uptake was also decreased by (in mM) 5 lactate, 5 methyl malonic acid, 1 alpha-cyano-4-hydroxycinnamate, and 1 mersalyl. Dissociated brain cells from 14- to 16-day-old rats accumulated 3-hydroxybutyrate at a rate more than two-fold greater than cells from either younger (2-day-old) or older (28-day-old and adult) animals. These data are consistent with the proposal that 3-hydroxybutyrate is taken up by the brain by both diffusion and a carrier-mediated transport system, and they support the hypothesis that transport at the cellular level contributes to the regulation of substrate utilization by the brain.


1979 ◽  
Vol 57 (s5) ◽  
pp. 111s-113s ◽  
Author(s):  
Claire Baxter ◽  
J. Horvath ◽  
G. Duggin ◽  
D. Tiller

1. Angiotensin II receptor binding was studied in specific regions of rat brain at different ages from birth to 14 weeks. 2. The number of specific angiotensin II receptors increased in all regions during the first 2 weeks of life and then decreased to adult levels. Peak numbers of receptors were up to 10 times the adult numbers. 3. The midbrain and thalamus-hypothalamus had maximum numbers of angiotensin II receptors at 2 weeks of age, whereas the rest of the brain regions had maximum numbers at 1 week. 4. Saralasin-infusion experiments suggested that circulating angiotensin-related peptides could reach brain angiotensin II receptors in 2 week old rats, but not in 6 week old rats. 5. It is postulated that the centrally mediated actions of circulating angiotensin II may be particularly important in the newborn.


Author(s):  
Hiroshi Yoshida ◽  
Yosuke Tsujishita ◽  
Françoise Hullin ◽  
Kimihisa Yoshida ◽  
Shun-Ichi Nakamura ◽  
...  

A Ca2+-independent phospholipase A that releases various fatty acids from sn-1 and sn-2 positions was partially purified from rat brain soluble fraction. The enzyme showed an approximate molecular mass of 300 kDa on gel filtration column chromatography. Its enzymatic properties are distinct from those of well characterized phospholipase A2 enzymes; by using a series of synthetic phosphatidylcholines, the enzyme cleaved oleic, linoleic, and arachidonic acids like phospholipase A2, and released palmitic and stearic acids like phospholipase A1. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid were hydrolysed with almost equal efficiencies by this enzyme. These results indicate that the enzyme isolated is a novel Ca2+ -independent intracellular phospholipase A that might be responsible for production of various fatty acids from membrane phospholipids.


1969 ◽  
Vol 112 (1) ◽  
pp. 29-33 ◽  
Author(s):  
P. S. Cheema ◽  
K. Malathi ◽  
G. Padmanaban ◽  
P. S. Sarma

Intraperitoneal administration of β-N-oxalyl-l-αβ-diaminopropionic acid, the neurotoxin from Lathyrus sativus, to 12-day-old rats causes typical convulsions within 10min. There is a striking accumulation of glutamine in the brain, and chronic ammonia toxicity is indicated. There are no changes in the amounts of urea, aspartic acid and glutamic acid in the brain. Adult rats, even when injected with a dose of excess of β-N-oxalyl-l-αβ-diaminopropionic acid, do not develop symptoms, and there are no changes in the amounts of glutamine or ammonia in the brain. A significant concentration of β-N-oxalyl-l-αβ-diaminopropionic acid can be detected in the brain of the young rat but not in that of the adult animal. It is concluded that β-N-oxalyl-l-αβ-diaminopropionic acid interferes with the ammonia-generating or -fixing mechanisms in the brain and leads to chronic ammonia toxicity.


2018 ◽  
Vol 8 (12) ◽  
pp. 2436 ◽  
Author(s):  
Mohamed H. M. Ali ◽  
Fazle Rakib ◽  
Volker Nischwitz ◽  
Ehsan Ullah ◽  
Raghvendra Mall ◽  
...  

Fourier Transform Infrared Spectroscopy (FTIR) is a non-destructive analytical technique that has been employed in this research to characterize the biochemical make-up of various rat brain regions. The sensorimotor cortex, caudate putamen, thalamus, and the hippocampus were found to have higher olefinic content—an indicator of a higher degree of unsaturated fatty acids—rich in short-chain fatty acids, and low in ester and lipid contents. While the regions of the corpus callosum, internal, and external capsule were found to contain long-chained and higher-esterified saturated fatty acids. These molecular differences may reflect the roles of the specific regions in information processing and can provide a unique biochemical platform for future studies on the earlier detection of pathology development in the brain, as a consequence of disease or injury. Laser Ablation Inductively Coupled Plasma Mass Spectroscopy (LA-ICP-MS) is another vital analytical technique that was used in this work to analyze the elements’ distribution patterns in various regions of the brain. The complementary data sets allowed the characterization of the brain regions, the chemical dominating groups, and the elemental composition. This set-up may be used for the investigation of changes in the brain caused by diseases and help create a deeper understanding of the interactions between the organic and elemental composition.


Author(s):  
D. E. Philpott ◽  
A. Takahashi

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.


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