Fatty Acid Incorporation in Normal and Degenerating Rat Sciatic Nerve <i>In Vivo</i>

Koeppen, Arnulf H.; Papandrea, John D.; Mitzen, Edward J.

doi:10.1111/j.1471-4159.1982.tb11491.x

Cited by 17 publications

(7 citation statements)

References 27 publications

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“…1) showed the expected developmental decrease during the course of this study (see Yao and Cannon, 1983). The apparent small decrease in acetate labeling at 3 days and the rebound at 1 week after crushing the contralateral nerve may be due to a retrograde transpinal effect (Koeppen et al, 1982;Yao, 1983;White et al, 1989).…”

Section: ['4c]acetate and ['Hlglycerol Incorporationmentioning

confidence: 52%

“…This equalization of activity at 15 weeks was not due to any further recovery of activity in the injured nerve, but rather to the continued maturational decline in activity in the control nerve. The small decrease in activity in the contralateral control nerve in the first week following the crush, as well as the rebound during the second week, may reflect a retrograde transpinal effect (Koeppen et al, 1982;Yao, 1983;White et al, 1989).…”

Section: Hmg-coa Reductase Activitymentioning

confidence: 96%

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Cholesterol Synthesis Is Down‐Regulated During Regeneration of Peripheral Nerve

Goodrum

1990

Journal of Neurochemistry

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The discovery of apolipoprotein E synthesis and secretion by injured peripheral nerve to the hypothesis that endoneurial apolipoprotein E serves to salvage degenerating myelin cholesterol. This salvaged cholesterol could then be reutilized by Schwann cells during remyelination via uptake through low-density lipoprotein receptors. As a test of this hypothesis, we measured the rate of cholesterol synthesis in rat sciatic nerve endoneurium during development and at various times following a crush injury at 50 days of age. In control nerves [14C]acetate incorporation into cholesterol and 3-hydroxy-3-methylglutaryl-CoA reductase activity were closely linked throughout development, indicating that reductase activity in nerve, as in other tissues, is a good indicator of cholesterol's synthetic rate. In the crushed nerves cholesterol synthesis fell to nearly zero during the first week after the crush. There was a partial recovery during the second to fourth weeks, but unlike that of other lipids, cholesterol synthesis remained well below control nerve values throughout most of the 15-week post-crush period examined. Thus, cholesterol synthesis is at very low levels during the myelination of regenerating axons. These results are consistent with a receptor-mediated down-regulation of cholesterol synthesis by lipoproteins, and would be expected if Schwann cells were utilizing an external source of cholesterol as postulated above.

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Section: ['4c]acetate and ['Hlglycerol Incorporationmentioning

confidence: 52%

Section: Hmg-coa Reductase Activitymentioning

confidence: 96%

Cholesterol Synthesis Is Down‐Regulated During Regeneration of Peripheral Nerve

Goodrum

1990

Journal of Neurochemistry

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“…These include decreased incorporation of acetate (Majno and Karnovsky, 1958;Rawlins and Smith, 1971;Natarajan et al, 1982) and increased incorporation of glycerol (Natarajan et al, 1982) into lipids, as well as preferential decreases in synthesis of myelin-enriched lipids such as sulfatides (Bourre et al, 1984) and cholesterol (Yao and Cannon, 1983). Increased incorporation of acetate into the free fatty acid pool (Koeppen et al, 1979) and increased labeling of cholesterol esters (Wood and Dawson, 1974;Belin and Smith, 1976;Yao et al, 1980 Yao andDyck, 1981;Koeppen et al, 1982) and triglycerides (Yao and Cannon, 1983;Yao, 1985) have also been reported during Wallerian degeneration.…”

Section: Discuss I 0 Nmentioning

confidence: 97%

“…Incorporation of [I4C]acetate into lipids in the proximal stump of transected sciatic nerve remained near control levels. The transient decrease in incorporation seen at 12 h in control nerve may be related to the effects of surgical trauma in the contralateral nerve; retrograde transpinal effects or humoral factors may be involved (Koeppen et al, 1982;Yao, 1983).…”

Section: Incorporation Of [I4c]acetate Into Lipidsmentioning

confidence: 98%

Lipid Metabolism During Early Stages of Wallerian Degeneration in the Rat Sciatic Nerve

White

Toews

Goodrum

et al. 1989

Journal of Neurochemistry

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We examined changes in biosynthetic capacity of sciatic nerve during the early stages of Wallerian degeneration, utilizing a model that permits exclusion of nonresident cells from degenerating nerve. Sciatic nerve segments were placed in either 5-microns pore (allowing infiltration of nonresident cells) or 0.22-microns pore (excluding nonresident cells) Millipore diffusion chambers and then implanted in the peritoneal cavity of the same 32-34-day-old rat. At times up to 7 days postsurgery, nerve segments from the chambers, as well as control segments from the contralateral sciatic nerve, were removed and their capacity to incorporate radioactive precursors into lipids and proteins assayed in vitro. In nerve segments from both the 0.22- and 5-microns pore chambers, incorporation of [14C]acetate into total lipids was decreased relative to control by 50% at 12 h postsurgery and by 85% at day 3. This decreased incorporation of [14C]acetate reflects primarily decreased de novo synthesis of cholesterol and of fatty acyl residues incorporated into glycerolipids and sphingolipids. There was a preferentially decreased synthesis of cerebrosides and cholesterol (components enriched in myelin) relative to other lipids, while cholesterol esters and free fatty acids (products of membrane degradation) accounted for a greater proportion of the greatly reduced levels of total lipid label. In contrast to [14C]acetate, incorporation of [3H]glycerol into lipids was increased up to fourfold, relative to control, 1 day after nerve transection.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…By analogy with the proposal (Fischer et al, 1982) for the role of the well-documented processes of the esterification of lyso-phospholipids (Baker and Thompson, 1972 ;Doherty and Rowe, 1979;Vaswani and Ledeen, 1989) and the transesterification of diacylglycerophospholipids Fischer et al, 1982;Koeppen et al, 1982) in nervous tissues, the direct acylation events observed here for the sphingolipids could be involved in the modification of the fatty acyl composition of these lipids and in regulating the concentration of lyso-sphingolipids and free fatty acids in the tissue, rather than in the net production of sphingolipids, which would be ensured via the ceramide pathway. In our study, we injected ['Hlpalmitate into sciatic nerves, thereby creating the situation where there is a locally increased level of free fatty acid, possibly at the level of the plasma membrane.…”

Section: The Direct Acylation Pathway Accounts For the Majority Of Spmentioning

confidence: 99%

Peripheral Nerve Sphingomyelin and Cerebroside are Both Formed Via two Metabolically and Kinetically Distinct Pathways In vivo

Heape

Boiron

Bessoule

et al. 1994

European Journal of Biochemistry

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We have studied the labeling kinetics of peripheral nerve sphingolipids in vivo. The kinetic analysis of the labeling profiles observed for the various sphingolipids demonstrated that 90% of cerebrosides, but only 30% of sphingomyelin, were synthesized via a de novo synthesized ceramide intermediate following the injection of 1-4 pmol [3H]palmitate into mouse sciatic nerves. The remaining sphingolipid labeling (30% of the total) was due to direct acylation events, using free fatty acids originating from a pool different from those implicated in the de novo ceramide pathway.Direct acylation events ceased within 1 h following substrate administration, while labeling via the ceramide pathway continued through 5 h. The results provide the first in vivo demonstration that the formation of cerebrosides and sphingomyelin in peripheral nerves in situ can be simultaneously assured via two metabolically and kinetically distinct pathways that employ different fatty acid pools.We recently demonstrated the synthesis of ceramides in peripheral nerves, both in vivo, following the intraneural injection of palmitate into the sciatic nerves of mice, and in vitro by a mouse sciatic nerve microsomal preparation in the presence of either stearoyl-CoA or lignoceroyl-CoA, and sphingosine, but not in the presence of free fatty acid (Boiron-Sargueil et al., 1992), as was previously observed for the central nervous system (Akanuma and Kishimoto, 1979;Morell and Radin, 1970; Singh and Kishimoto, 1979). No information is available concerning the fate of ceramides in peripheral nerves, while in the central nervous system, in vivo (Carter and Kanfer, 1974) and in vitro (Akanuma and Kishimoto, 1979;Morell and Radin, 1969; Singh and Kishimoto, 1979; Ullman and Radin, 1972) studies have led to conflicting conclusions with respect to the participation of ceramides and galactosylsphingosine (psychosine) in the formation of hydroxylated and nonhydroxylated galactocerebrosides. Similarly, sphingomyelin synthesis has been proposed to occur via the transfer of phosphocholine from CDP-choline, or phosphatidylcholine, to ceramide, and by the condensation of sphingosine phosphocholine with fatty acyl-CoA (Kishimoto, 1983;Sweely, 1991;Spence, 1993).In this paper, we have administered a small amount of an exogenous labeled substrate that is rapidly incorporated into the natural lipid metabolic pathways of mouse sciatic nerves, and studied the fate of the resulting labeled products, in order to identify metabolic precursors of the sphingolipids in this system, and hence to clarify the situation with respect to the pathways implicated in their biosynthesis in situ. Under the conditions that we have established for the in vivo study of peripheral nerve lipid metabolism (Heape et al., 1989(Heape et al., , 1990, the very rapid and almost complete utilisation of the small quantity of substrate administered to the nerves gives access to both the short-term and long-term metabolisms of the labeled exogenous substrate and, hence, to the formation of the metabolic...

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Fatty Acid Incorporation in Normal and Degenerating Rat Sciatic Nerve In Vivo

Cited by 17 publications

References 27 publications

Cholesterol Synthesis Is Down‐Regulated During Regeneration of Peripheral Nerve

Cholesterol Synthesis Is Down‐Regulated During Regeneration of Peripheral Nerve

Lipid Metabolism During Early Stages of Wallerian Degeneration in the Rat Sciatic Nerve

Peripheral Nerve Sphingomyelin and Cerebroside are Both Formed Via two Metabolically and Kinetically Distinct Pathways In vivo

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