Differential gene expression during development in two oligodendroglial cell lines overexpressing transferrin: a cDNA array analysis.
In the central nervous system, transferrin (Tf) is produced by oligodendroglial cells (OLGcs) and is essential for their development. Recently, using the complete cDNA of the human Tf gene, we obtained clones overexpressing Tf in two OLGc lines, N19 and N20.1, which represent different stages of differentiation. We showed that the overexpression of this glycoprotein promotes the maturation and myelinogenic capacity of both cell lines. In this work, using cDNA array technology, we examined changes induced by Tf in 1,176 genes. We found 41 genes differentially expressed in both cell lines, all of them involved in OLGc development. In the less mature cells (N19) overexpressing Tf, there was a significant increase in key enzymes of neurosteroid metabolism, such as cholesterol side chain cleavage cytochrome P450, 3beta-hydroxysteroid dehydrogenase and 5alpha-reductase type 1. In the more mature cell line (N20.1), Tf overexpression produced an induction of several mRNAs of the GABA(A) receptor subunits, of thyroid hormone receptors and of proteins involved in axon-glia interactions such as F3/contactin. In addition, in both cell lines, Tf overexpression induced an increase in the expression of different isoforms of transforming growth factor beta receptors and in several genes related to mitochondrial function and to complex lipid metabolism, crucial steps in myelin synthesis. Differentiation produced by Tf in both cell lines seems to occur by modulation of different genes depending on the maturational stage of the cells. Our findings provide new insights into the molecular basis of OLGc differentiation and on the role played by Tf in this process.
García
Corina I
CI
Instituto de Química y Fisicoquímica Biológica (IQUIFIB), UBA-CONICET, y Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Paez
Pablo M
PM
Soto
Eduardo F
EF
Pasquini
Juana M
JM
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics; D042944:Cholestenone 5 alpha-Reductase / Q000235:genetics; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D050356:Lipid Metabolism; D024101:Mitochondrial Proteins / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D013256:Steroids / Q000378:metabolism; D014168:Transferrin / Q000235:genetics / Q000502:physiology*
D007527:Isoenzymes; D024101:Mitochondrial Proteins; D013256:Steroids; D014168:Transferrin; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D042944:Cholestenone 5 alpha-Reductase