PubMed Health⌕ Search

Biomedical subjects

J M Matthieu

Publications and source records attributed to J M Matthieu.

At least 109 records · Page 6Linked to original sources
PubMed1981

Lipid metabolism and oxygen consumption in a hereditary demyelinating neuropathy, the trembler mouse: an in vitro study.

Sciatic nerves from 15-day-old trembler and control mice were maintained in vitro up to 53 h and the metabolism of myelin lipids and the oxygen consumption were investigated [35S]Sulfate was incorporated into sulfatides at a higher rate and turned over more rapidly in trembler nerves than in controls. [14C]Galactose was incorporated into cerebrosides of trembler nerves at a lower rate and turned over like the controls. In contrast, synthesis of sulfatides labeled with [14]galactose was increased in mutants and no significant turnover was observed for both trembler and control nerves during the whole incubation period. Similar results were obtained using [3H]serine as a precursor and no significant differences were observed in the turnover rates of sphingomyelin and phosphatidylcholine between trembler and control nerves. These data suggest the presence of two different pools of cerebrosides, a small one formed by the fast recycling of sulfatides and which does not mix with a second, larger one. The rate of oxygen consumption did not change significantly during the incubation period and was 2-3-fold higher in trembler nerves than in controls, reflecting, at least partly, the increased sulfatide metabolism.

Animals↗
PubMed1981

Similarities and dissimilarities between two myelin deficient mutant mice, Shiverer and mld.

In the brain of Shiverer and mld mutant mice, myelin is poorly compacted and the major dense line of the myelin is practically missing. Major biochemical differences were detected between mutations. In mld myelin, myelin basic proteins are mainly affected and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) exhibits a very high specific activity. In Shiverer myelin, in addition to basic proteins, all major myelin proteins are also decreased while CNP specific activity is moderately increased.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1981

Myelin proteins, glycoproteins, and myelin-related enzymes in experimental demyelination of the rabbit optic nerve: sequence of events.

Wallerian degeneration of the rabbit optic nerve was investigated by the technique of retinal ablation which precludes edema, hemorrhage, or macrophage infiltration. After 8 days of degeneration, marked degradation of axons and some myelin abnormalities appeared in the optic nerve, optic chiasma, and optic tract. Myelin lesions were maximal 32 days after retinal destruction. The amount of material stained with a myelin dye decreased drastically between 32 and 90 days after the operation. Biochemical parameters gave the following sequence of events. The concentration of the major periodic acid--Schiff staining glycoproteins was decreased after 2 days, and 6 days later the presence of cholesterol esters was detected in the optic tissue. After 16 days of Wallerian degeneration, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase not associated with myelin decreased, indicating a possible de-differentiation of oligodendrocytes. Degradation of myelin basic protein became significant at 32 days and the amount of myelin isolated decreased later. The loss of myelin basic protein coincided with a reduction of myelin periodicity as measured in purified fractions by electron microscopy. These results show that secondary myelin destruction in the absence of edema, hemorrhage, or macrophages is a very slow process, and in this situation myelin undergoes a selective and sequential loss of its constituents.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1981

Effects of colchicine on myelination of rabbit optic nerve: a biochemical study.

The effects of intravitreous injections of colchicine on the myelination of the optic nerve were studied in rabbits at different times during development using biochemical and morphological techniques. Myelin basic protein concentrations and 2',3-cyclic nucleotide 3'-phosphodiesterase activities were affected in a similar way by colchicine treatment and reflected the degree of myelination of the tissue. During early development, colchicine produced axonal degeneration and secondary demyelination (Wallerian degeneration). Later, axonal and myelin abnormalities were more variable. Some demyelination was observed amd myelin formation also may have been inhibited. Thus, the effect of colchicine was proportional to the degree of optic nerve and retinal maturation (the youngest being the most sensitive) and, to a lesser extent, to the dosage, Under conditions used for this study, no remyelination was observed. In adult animals, no lesions could be detected histologically one to four months after injection of colchicine, Thus, intravitreous administration of colchicine is a useful chemical technique for producing Wallerian degeneration in optic nerves of young developing rabbits.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1980

Abnormal sulfate metabolism in a hereditary demyelinating neuropathy.

Trembler mice are affected by dominantly inherited neuropathy. Total lipid content and sulfatides were decreased in peripheral nerves from 15-day-old mutants. The proportion of sulfatides in per cent of total lipids was similar in control and Trembler nerves. The specific activity of ceramide galactosyltrnsferase, the enzyme responsible for the synthesis of cerebrosides, was 36 and 13% of controls, in young and adult. Trembler nerves, respectively. In contrast, cerebroside sulfotransferase activities were increased by 257 and 172% in young and adult Trembler sciatic nerves, respectively. No activator or inhibitor effect could be demonstrated. In Trembler PNS, Km, Vmax and heat sensitivity of CST differed from controls. Low levels of substrate and high arylsulfatase A activity (218% of controls) could explain the lack of sulfatide accumulation. The increased in vivo sulfate and galactose incorporation into non-lipidic material couild reflect the overproduction of endoneurial and perineurial connective tissue, whereas the high turnover rate of sulfatides could be correlated with intense demyelination and remyelination observed in Trembler PNS.

Animals↗
PubMed1980

Evidence for the association of 2',3'-cyclic-nucleotide 3'-phosphodiesterase with myelin-related membranes in peripheral nervous system.

In PNS, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in myelin was not enriched over the starting homogenate. Nevertheless, most of the total activity was recovered in myelin. In myelin-deficient mutants, low CNP activities were measured in sciatic nerves. CNP specific activities were similar in myelinated and non-myelinated nerves but in non-nervous tissues, they were significantly lower than in nervous tissue. There was no indication for the presence of an isoenzyme of CNP in peripheral nerves. These results indicate that CNP is present in PNS myelin and preferentially localized in Schwann cell plasma membranes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

Distribution of PNS myelin proteins and membrane enzymes in fractions isolated by continuous gradient zonal centrifugation.

Myelin was purified from adult rabbit sciatic nerve by two procedures: discontinuous gradient centrifugation and continuous gradient zonal centrifugation. Two fractions were obtained from the discontinuous gradient. The fraction floating on 0.32 M sucrose and the fraction recovered from the 0.32/0.85 M sucrose interface showed typical myelin membranes by electron microscopy and typical myelin proteins by gel electrophoresis. The specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased from the top to the bottom of the discontinuous gradient. The myelin separated by zonal centrifugation on a continuous sucrose gradient showed three distinct peaks (on monitoring optical density) at 0.10, 0.30 and 0.57 M sucrose. The latter peak yielded 92% of the material applied. The two minor peaks of low density exhibited high CNP and acetylcholinesterase (AChE) activities but the specific activity of both enzymes increased markedly at the heavy end of the gradient. The zonal fractions showed typical myelin proteins in all fractions by polyacrylamide gel electrophoresis but with important quantitative differences. These results indicate that PNS myelin shows significant heterogeneity.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

The lipid composition of rat brain aggregating cell cultures during development.

The lipid and fatty acid composition of rat brain was studied during its development both in vivo and in an aggregating cell culture system. Although the amount of lipid present in the cultures was very low, the increase in glycolipid content corresponded closely to the period of intense myelin formation. Very long chain fatty acids (hydroxylated and unsubstituted) were present in 41-day cultures. In comparison to the in vivo situation, myelination was delayed in vitro and, after 40 days in culture, cholesterol esters were 5-fold higher than in vivo, indicating that demyelination was occurring.

Animals↗
PubMed1978

Proteins from sciatic-nerve myelin in quaking and jimpy mice.

Myelin from two neurological mutants in mice was isolated from sciatic nerves and its protein composition analysed. In Quaking mice, two intrinsic myelin proteins P1 and P2 were drastically decreased, whereas the major myelin protein P0 was unaffected. A normal protein composition was found in sciatic myelin from Jimpy mice.

Animals↗
PubMed1978

Protein and enzyme distribution in microsomal and myelin fractions from rat and Jimpy mouse brain.

The protein, glycoprotein and enzyme composition of myelin and myelin-related fraction (SN 4) from rat forebrain was compared with that of microsomal fractions. Acetylcholinesterase was largely confined to the microsomal fractions, wheras 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) showed a high specific activity in myelin and SN 4 fractions. Nevertheless, the total specific activities of CNP present in microsomal membranes and in a water-soluble form were not negligible, and suggest that this enzyme has a wide distribution among subcellular particles. A high molecular weight protein was identified in myelin and all the other fractions studied. This protein (X), which co-migrates with the major myelin glycoprotein, was present in myelin and in fractions lacking typical myelin components as well as in fractions from a myelin deficient mutant, the Jimpy mouse. The results suggest that the X protein is probably a contaminant in isolated myelin, although the occurrence of this protein as an intrinsic component of several different membranes cannot be ruled out. Despite substantial overlap in density upon zonal centrifugation between SN 4 and microsomal fractions, the enzyme patterns of the fractions were different.

Acetylcholinesterase↗
PubMed1978

Isolation and partial characterization of rat CNS axolemma enriched fractions.

Axolemma-enriched fractions were prepared from rat brain by osmotic shock of a purified preparation of myelinated axons and subsequent separation of myelin, two axolemma-enriched fractions and myelin-free axons by density gradient centrifugation. Compared with the starting whole homogenate, the fractions were enriched in specific activity of Na+K+ ATPase, acetylcholinesterase, 5'nucleotidase as well as 2',3'-cyclic nucleotide 3'phosphohydrolase. Compared with myelin, the axolemmal fractions are greatly enriched in high molecular weight proteins. The 1.0/1.2 fraction has a predominant peak of fucose-labeled glycoprotein with a molecular weight between that of the myelin associated glycoprotein and the Wolfgram protein which is absent from the myelin glycoprotein profile. Polyacrylamide gel electrophoresis showed that the protein profile of myelin isolated by this procedure was similar to that of myelin isolated by other procedures and that the myelin specific basic and proteolipid proteins were virtually absent in the axolemma-enriched fractions. Both axolemma fractions were enriched in higher MW proteins, some of which resembled proteins in the myelin protein profile. Both axolemma-enriched fractions specifically bind between 2 and 3 pmoles of [3H]tetrodotoxin per mg protein. The axolemma-enriched fractions incorporated [3H]leucine and [14C]fucose exclusively into high molecular weight proteins and glycoproteins. In contrast myelin concomitantly isolated with the axolemma-enriched fractions had a significant amount of [3H]leucine labeled protein in myelin proteolipid and basic proteins. In addition to the myelin associated g-ycoprotein the [14C]fucose labeled a glycoprotein of slightly larger apparent molecular weight than proteolipid protein was found in the myelin fraction while the comparable labeled glycoprotein was absent in the axolemma-enriched fractions. The possible extent of contamination of these fractions by myelin or myelin subfractions and relationship of these axolemma-enriched fractions to other axolemma preparations are discussed.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1978

In vivo incorporation of 32P into myelin basic protein from normal and quaking mice.

Myelin basic protein in normal mice is phosphorylated. Since phosphorylation can decrease the net positive charge of the myelin basic protein, this could affect molecular interactions between this protein and other myelin components. In this study 32P incorporation into small and large components of the myelin basic protein was studied in immature and young adult mice and also in Quaking mutants which have a severe myelin deficit. We found a short half-life of 32P in myelin basic protein. The 32P specific activity of myelin basic protein was higher in immature and Quaking mice than in young adult animals. Of the 32P-labeled basic proteins of control and Quaking mice, the small component had a slightly higher specific activity than the large component. Although the small basic protein is quantitatively decreased in Quaking mice, the ratio of specific activity of small to large basic protein is similar in control and Quaking animals. Since Quaking and immature mice have many uncompacted myelin lamellae, these preliminary results suggest that phosphorylation and dephosphorylation could be involved in compaction mechanisms.

Aging↗