Primary demyelination induced by exposure to tellurium alters mRNA levels for nerve growth factor receptor, SCIP, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and myelin proteolipid protein in rat sciatic nerve.
Weanling rats fed a diet containing tellurium develop a peripheral neuropathy characterized by a highly synchronous primary demyelination; this demyelination is followed closely by a period of rapid remyelination. The demyelination is related to the inhibition of squalene epoxidase activity, which results in a block in cholesterol synthesis. Expression of mRNA for the major structural proteins of PNS myelin, myelin basic protein and P0, is coordinately down-regulated during the demyelinating phase and then up-regulated during the remyelinating phase (Toews et al., J. Neurosci. Res., 26 (1990) 501-507). We now report tellurium-induced alterations in gene expression for several proteins which are not major structural components of myelin in the peripheral nervous system. Expression of mRNA for nerve growth factor receptor in sciatic nerve was very low in control animals, but was markedly up-regulated after 3-5 days of exposure to tellurium, a time corresponding to the beginning of demyelination. Levels remained elevated during the subsequent period of remyelination. Expression of mRNA for SCIP (a presumptive transcription factor) was also up-regulated in sciatic nerve following tellurium exposure, with a time course similar to that for nerve growth factor receptor. When examined as a fraction of total RNA, steady-state mRNA levels for 2',3'-cyclic nucleotide 3'-phosphodiesterase and the myelin proteolipid protein were decreased during the demyelinating phase; however, this decrease could be largely accounted for by increased levels of total RNA. When analyzed on a 'per nerve' basis, steady-state mRNA levels for these two proteins were actually increased about 2-fold by 9 days after beginning tellurium exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Toews
A D
AD
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
Eckermann
C E
CE
Roberson
M D
MD
Lee
S Y
SY
Morell
P
P
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D050816:Octamer Transcription Factor-6; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013691:Tellurium / Q000633:toxicity*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C494179:Pou3f1 protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D013691:Tellurium