Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit

Effect of S-adenosylmethionine

Roberto Bianchi, Federico Calzi, Sara Savaresi, Roberto Sciarretta-Birolo, Raffaele Bellasio, Virginia Tsankova, Maria Teresa Tacconi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

S-Adenosylmethionine (SAMe) is the methyl donor to numerous acceptor molecules. We used cycloleucine (CL), which prevents the conversion of methionine to SAMe by inhibiting ATP-L-methionine-adenosyltransferase (MAT), to characterize the lipid and protein changes induced in peripheral nerve and brain myelin in rats during development. We also investigated the effect of exogenous SAMe by administering SAMe-1,4-butane disulfonate (SAMe-SD4). CL was given on days 7, 8, 12, and 13 and SAMe-SD4 was given daily from day 7; the animals were killed on day 18. CL accumulates in the brain reaching a concentration within 24 h compatible with its ID50 in vitro and interacting with methionine metabolism; brain MAT activity and SAMe levels were lower and methionine levels higher than in controls. CL significantly reduced brain and nerve weight gains, brain myelin content, proteins, phospholipids, and galactolipids. Among phospholipids in nerve and brain, only sphingomyelin was significantly increased, by 35-50%. Sciatic nerve protein analyses showed some significant changes: protein zero in sciatic nerve remained unchanged but the 14.0- and 18.5-kDa isoforms of myelin basic protein showed a dramatic increase. Among the main proteins, in purified brain myelin, the proteolipid protein and dimer-20 isoform decreased after CL. SAMe-SD4 highlights some sensitive parameters by counteracting, at least partially, some alterations of PL - particularly galactolipids and sphingomyelins - and proteins induced by CL. The partial beneficial effects might also be explained by the age- related limited bioavailability of exogenous SAMe, a finding, to our knowledge, not yet reported elsewhere. This study demonstrates that availability of methyl donors is closely related to the formation of myelin components.

Original languageEnglish
Pages (from-to)258-266
Number of pages9
JournalExperimental Neurology
Volume159
Issue number1
DOIs
Publication statusPublished - Sep 1999

Fingerprint

Myelin Proteins
S-Adenosylmethionine
Cycloleucine
Lipids
Methionine
Brain
Methionine Adenosyltransferase
Galactolipids
Sphingomyelins
Sciatic Nerve
Myelin Sheath
Proteins
Phospholipids
Myelin Proteolipid Protein
Myelin Basic Protein
Peripheral Nerves
Biological Availability
Weight Gain
Protein Isoforms
Adenosine Triphosphate

Keywords

  • Brain
  • Cycloleucine
  • Hypomyelination
  • Myelin lipid
  • Myelin protein
  • Rat
  • Sciatic nerve

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Bianchi, R., Calzi, F., Savaresi, S., Sciarretta-Birolo, R., Bellasio, R., Tsankova, V., & Tacconi, M. T. (1999). Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit: Effect of S-adenosylmethionine. Experimental Neurology, 159(1), 258-266. https://doi.org/10.1006/exnr.1999.7132

Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit : Effect of S-adenosylmethionine. / Bianchi, Roberto; Calzi, Federico; Savaresi, Sara; Sciarretta-Birolo, Roberto; Bellasio, Raffaele; Tsankova, Virginia; Tacconi, Maria Teresa.

In: Experimental Neurology, Vol. 159, No. 1, 09.1999, p. 258-266.

Research output: Contribution to journalArticle

Bianchi, R, Calzi, F, Savaresi, S, Sciarretta-Birolo, R, Bellasio, R, Tsankova, V & Tacconi, MT 1999, 'Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit: Effect of S-adenosylmethionine', Experimental Neurology, vol. 159, no. 1, pp. 258-266. https://doi.org/10.1006/exnr.1999.7132
Bianchi, Roberto ; Calzi, Federico ; Savaresi, Sara ; Sciarretta-Birolo, Roberto ; Bellasio, Raffaele ; Tsankova, Virginia ; Tacconi, Maria Teresa. / Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit : Effect of S-adenosylmethionine. In: Experimental Neurology. 1999 ; Vol. 159, No. 1. pp. 258-266.
@article{e70d112e5b3d43ed9f99c712c119855f,
title = "Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit: Effect of S-adenosylmethionine",
abstract = "S-Adenosylmethionine (SAMe) is the methyl donor to numerous acceptor molecules. We used cycloleucine (CL), which prevents the conversion of methionine to SAMe by inhibiting ATP-L-methionine-adenosyltransferase (MAT), to characterize the lipid and protein changes induced in peripheral nerve and brain myelin in rats during development. We also investigated the effect of exogenous SAMe by administering SAMe-1,4-butane disulfonate (SAMe-SD4). CL was given on days 7, 8, 12, and 13 and SAMe-SD4 was given daily from day 7; the animals were killed on day 18. CL accumulates in the brain reaching a concentration within 24 h compatible with its ID50 in vitro and interacting with methionine metabolism; brain MAT activity and SAMe levels were lower and methionine levels higher than in controls. CL significantly reduced brain and nerve weight gains, brain myelin content, proteins, phospholipids, and galactolipids. Among phospholipids in nerve and brain, only sphingomyelin was significantly increased, by 35-50{\%}. Sciatic nerve protein analyses showed some significant changes: protein zero in sciatic nerve remained unchanged but the 14.0- and 18.5-kDa isoforms of myelin basic protein showed a dramatic increase. Among the main proteins, in purified brain myelin, the proteolipid protein and dimer-20 isoform decreased after CL. SAMe-SD4 highlights some sensitive parameters by counteracting, at least partially, some alterations of PL - particularly galactolipids and sphingomyelins - and proteins induced by CL. The partial beneficial effects might also be explained by the age- related limited bioavailability of exogenous SAMe, a finding, to our knowledge, not yet reported elsewhere. This study demonstrates that availability of methyl donors is closely related to the formation of myelin components.",
keywords = "Brain, Cycloleucine, Hypomyelination, Myelin lipid, Myelin protein, Rat, Sciatic nerve",
author = "Roberto Bianchi and Federico Calzi and Sara Savaresi and Roberto Sciarretta-Birolo and Raffaele Bellasio and Virginia Tsankova and Tacconi, {Maria Teresa}",
year = "1999",
month = "9",
doi = "10.1006/exnr.1999.7132",
language = "English",
volume = "159",
pages = "258--266",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Biochemical analysis of myelin lipids and proteins in a model of methyl donor pathway deficit

T2 - Effect of S-adenosylmethionine

AU - Bianchi, Roberto

AU - Calzi, Federico

AU - Savaresi, Sara

AU - Sciarretta-Birolo, Roberto

AU - Bellasio, Raffaele

AU - Tsankova, Virginia

AU - Tacconi, Maria Teresa

PY - 1999/9

Y1 - 1999/9

N2 - S-Adenosylmethionine (SAMe) is the methyl donor to numerous acceptor molecules. We used cycloleucine (CL), which prevents the conversion of methionine to SAMe by inhibiting ATP-L-methionine-adenosyltransferase (MAT), to characterize the lipid and protein changes induced in peripheral nerve and brain myelin in rats during development. We also investigated the effect of exogenous SAMe by administering SAMe-1,4-butane disulfonate (SAMe-SD4). CL was given on days 7, 8, 12, and 13 and SAMe-SD4 was given daily from day 7; the animals were killed on day 18. CL accumulates in the brain reaching a concentration within 24 h compatible with its ID50 in vitro and interacting with methionine metabolism; brain MAT activity and SAMe levels were lower and methionine levels higher than in controls. CL significantly reduced brain and nerve weight gains, brain myelin content, proteins, phospholipids, and galactolipids. Among phospholipids in nerve and brain, only sphingomyelin was significantly increased, by 35-50%. Sciatic nerve protein analyses showed some significant changes: protein zero in sciatic nerve remained unchanged but the 14.0- and 18.5-kDa isoforms of myelin basic protein showed a dramatic increase. Among the main proteins, in purified brain myelin, the proteolipid protein and dimer-20 isoform decreased after CL. SAMe-SD4 highlights some sensitive parameters by counteracting, at least partially, some alterations of PL - particularly galactolipids and sphingomyelins - and proteins induced by CL. The partial beneficial effects might also be explained by the age- related limited bioavailability of exogenous SAMe, a finding, to our knowledge, not yet reported elsewhere. This study demonstrates that availability of methyl donors is closely related to the formation of myelin components.

AB - S-Adenosylmethionine (SAMe) is the methyl donor to numerous acceptor molecules. We used cycloleucine (CL), which prevents the conversion of methionine to SAMe by inhibiting ATP-L-methionine-adenosyltransferase (MAT), to characterize the lipid and protein changes induced in peripheral nerve and brain myelin in rats during development. We also investigated the effect of exogenous SAMe by administering SAMe-1,4-butane disulfonate (SAMe-SD4). CL was given on days 7, 8, 12, and 13 and SAMe-SD4 was given daily from day 7; the animals were killed on day 18. CL accumulates in the brain reaching a concentration within 24 h compatible with its ID50 in vitro and interacting with methionine metabolism; brain MAT activity and SAMe levels were lower and methionine levels higher than in controls. CL significantly reduced brain and nerve weight gains, brain myelin content, proteins, phospholipids, and galactolipids. Among phospholipids in nerve and brain, only sphingomyelin was significantly increased, by 35-50%. Sciatic nerve protein analyses showed some significant changes: protein zero in sciatic nerve remained unchanged but the 14.0- and 18.5-kDa isoforms of myelin basic protein showed a dramatic increase. Among the main proteins, in purified brain myelin, the proteolipid protein and dimer-20 isoform decreased after CL. SAMe-SD4 highlights some sensitive parameters by counteracting, at least partially, some alterations of PL - particularly galactolipids and sphingomyelins - and proteins induced by CL. The partial beneficial effects might also be explained by the age- related limited bioavailability of exogenous SAMe, a finding, to our knowledge, not yet reported elsewhere. This study demonstrates that availability of methyl donors is closely related to the formation of myelin components.

KW - Brain

KW - Cycloleucine

KW - Hypomyelination

KW - Myelin lipid

KW - Myelin protein

KW - Rat

KW - Sciatic nerve

UR - http://www.scopus.com/inward/record.url?scp=0032853672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032853672&partnerID=8YFLogxK

U2 - 10.1006/exnr.1999.7132

DO - 10.1006/exnr.1999.7132

M3 - Article

VL - 159

SP - 258

EP - 266

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 1

ER -