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 language | English |
|---|---|
| Pages (from-to) | 258-266 |
| Number of pages | 9 |
| Journal | Experimental Neurology |
| Volume | 159 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Sep 1999 |
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Keywords
- Brain
- Cycloleucine
- Hypomyelination
- Myelin lipid
- Myelin protein
- Rat
- Sciatic nerve
ASJC Scopus subject areas
- Neurology
- Neuroscience(all)
Cite this
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 journal › Article
}
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 -