Cell‐type specific segregation of transcriptional expression of glial genes in the rat peripheral neurotumor RT4 cell lines

Hagiwara, Nobuko; Imada, Sumi; Sueoka, Noboru

doi:10.1002/jnr.490360605

Cited by 20 publications

(16 citation statements)

References 57 publications

(69 reference statements)

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“…Our work on the RT4 cell lines RT4-AC36A and RT4-D6 has shown that dibutyryl-cAMP or forskolin treatment enhances expression levels of GFAP (11,13), S100,1 (7,11,13), suppressed cAMP inducible POU (SCIP), protein P0, and 2',3'-cyclic 3'-nucleotide phosphodiesterase (14), increases high-affinity y-aminobutyric acid uptake (10), and weakly induces myelin basic protein (MBP) in RT4-AC36A and strongly in RT4-D6 cells (14,15). The concurrent stimulation of the expression of these glial genes by cAMP indicates that intracellular cAMP may act as a general regulatory factor in the induction of glial maturation both in vivo and in culture.…”

Section: Resultsmentioning

confidence: 93%

“…The neuronal-cell types RT4-B and RT4-E exhibit only neuronal characteristics: voltage-dependent Na+ and K+ channels (7)(8)(9) and process extension in response to dibutyryl-cAMP and testololactone treatment (10). The glialcell type RT4-D so far exhibits only glial characteristics: the transcriptional expression of the genes for S100, (7,11,12), GFAP (11,13), protein P0 (14), SCIP (suppressed cAMPinducible POU, a protein containing the POU-domain) (14), the 2.8-kb form of 2',3'-cyclic 3'-nucleotide phosphodiesterase (CNP) mRNA (14), and MBP (myelin basic protein) (14,15). All of these glial genes are responsive to cAMP (11,14).…”

mentioning

confidence: 99%

“…The glialcell type RT4-D so far exhibits only glial characteristics: the transcriptional expression of the genes for S100, (7,11,12), GFAP (11,13), protein P0 (14), SCIP (suppressed cAMPinducible POU, a protein containing the POU-domain) (14), the 2.8-kb form of 2',3'-cyclic 3'-nucleotide phosphodiesterase (CNP) mRNA (14), and MBP (myelin basic protein) (14,15). All of these glial genes are responsive to cAMP (11,14). The expression of GFAP in the stem-cell type RT4-AC and the glial-cell type RT4-D is stimulated by long-term treatment with dibutyryl-cAMP, forskolin, or cholera toxin (11,13) as in the case of cultured astrocytes (16,17) and the rat glioma cell line C6 (18).…”

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confidence: 99%

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Glial-specific cAMP response of the glial fibrillary acidic protein gene cell lines.

Kaneko

Hagiwara

Leader

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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Expression of the rat glial fibrillary acidic protein (GFAP) gene is responsive to the intracellular level of cAMP. We have examined the sequence 5'-upstream of the transcription start site of the rat GFAP-encoding gene to determine the elements responsible for regulating the cAMP response. The RT4 cell lines consist of a neural stem-cell type RT4-AC and its three derivative cell types, one glial-cell type, RT4-D, and two neuronal-cell types, RT4-B and RT4-E. GFAP is expressed in the stem-cell type and the glial-cell type but is not expressed in the neuronal-cell types. Luciferase expression vectors containing various areas of the 10.8-kb region upstream ofthe transcription start site ofthe GFAP gene were transiently transfected into these RT4 cells. The effect of cAMP was examined by quantitating the transient expression of luciferase. We found that (s) the 5'-upstream region alone (up to 10.8 kb) allows expression of the GFAP gene in the stem-cell type, the glial-cell type, and a neuronal-cell type; (it) there are negative and positive cAMP-responsive elements that are juxtaposed within the region between -240 bp and -110 bp upstream and are functional in the stem-cell and glial-cell types but are not functional in the neuronal-cell type RT4-E; (Mi) there may be elements that respond to dibutyryl-cAMP in all three RT4 cell types within the region from 2 kb to 10.8 kb upstream of the transcription start site; and (iv) a regulatory luciferase plasmid pRLgfap-1, containing both the upstream and downstream regulatory regions of the GFAP gene, not only expresses luciferase but also responds to forskolin in the stem-cell type and the glial-cell type. This regulatory plasmid, however, does not express in the neuronal-cell type with or without the forskolin treatment.

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Section: Resultsmentioning

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Glial-specific cAMP response of the glial fibrillary acidic protein gene cell lines.

Kaneko

Hagiwara

Leader

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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“…Forskolin increases cAMP by activating adenylate cyclase while IBMX inhibits cAMP degradation [Seamon and Daly, 1986]. Also, Hagiwara et al [1993] have shown that forskolin treatment of AC36A stem and D6 glial cells elevates the levels of mRNA for PO, SCIP, CNP, myelin basic protein and low-affinity nerve growth factor recep tor. Subconfluent RT4-AC36A, D6 and E5 cells were cul tured for either 6 or 24 h in the presence of 25 (iiV/ forsko lin and 0.5 mM IBMX.…”

Section: Figmentioning

confidence: 99%

“…After cell type conversion, only glial properties are expressed (i.e. segregate) in RT4-D (GFAP, SlOOp, PO, CNP, loss of Na+ and K+ channels and membrane excitability), while neuronal properties segregate only in RT4-E and RT4-B (retention of voltage-sensitive Na+ and K+ channels and membrane excitability, loss of GFAP, SlOOp, PO and CNP) [Tomozawaand Sueoka, 1978;Dromsand Sueoka, 1987;Hagiwara et al, 1993]. In this report, we show that in subconfiuent cells the expression of CKB mRNA and enzyme was high both in the progenitor RT4-AC36A and glial RT4-D6 cells but was dramatically lower in neuronal RT4-E5 cells and was undetectable in neuronal RT4-B8 cells.…”

Section: Introductionmentioning

confidence: 99%

Expression of the Brain Creatine Kinase Gene in Rat RT4 Peripheral Neurotumor Cell Lines and Its Modulation by Cell Confluence

Wilson

Shen²,

Kuzhikandathil³

et al. 1997

Dev Neurosci

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Creatine kinases (CK) catalyze the reversible transfer of a high energy phosphate group between creatine phosphate and ADP to regenerate ATP in cell types where the requirements for ATP are extensive and/or sudden. Previously, we have shown in primary rat brain cell cultures that brain CK (CKB) mRNA levels are highest in astrocytes and oligodendrocytes and much lower in neuronal cells. However, little is known of the factors which regulate CKB expression in the central nervous system and peripheral nervous system. To begin to investigate these factors, we asked in this report (1) if this pattern of CKB expression was also characteristic of some established glial and neuronal cell lines derived from the PNS; (2) whether CKB expression could be rapidly modulated by culture conditions, and (3) if CKB is expressed in cells with characteristics of glial cell progenitors. In subconfluent cells, CKB mRNA and enzyme activity were found to be high in both the rat RT4 peripheral neurotumor stem cell RT4-AC36A and its glial cell derivative RT4-D6. Conversely, CKB mRNA and activity were 5- and 8-fold lower, respectively, in the neuronal derivative RT4-E5 and, more dramatically, CKB was undetectable in neuronal RT4-B8 cells. Maintaining RT4-D6 glial cells at confluence rapidly increased CKB enzyme activity by 7-fold, such that D6 cells contained about 25% of the CKB level in lysates prepared from either whole adult rat brain or primary cultures of rat brain astrocytes. The levels of CKB mRNA and immunoreactive protein were also correspondingly increased in confluent D6 cells. These confluence-mediated increases in CKB appeared to be due to cell-cell contact and not the depletion of serum growth factors or an increase in intra-cellular cAMP. This study indicates that CKB expression is highest in cells displaying glial properties and can be rapidly modulated by appropriate culture conditions. The results are discussed in relation to the factors which may regulate CKB expression in vivo.

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Expression of the myelin basic protein gene locus in neurons and oligodendrocytes in the human fetal central nervous system

et al. 1996

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The myelin basic protein (MBP) gene locus is composed of two overlapping transcription units that share all of the MBP exons. One of these transcription units expresses the MBPs and the other expresses a family of proteins structurally related to the MBPs. This second transcription unit is called the Golli gene, and the entire complex is called the Golli-mbp gene. In this study, the expression of the Golli gene was examined in the human fetal central nervous system (CNS). By using reverse transcriptase-polymerase chain reaction cloning we have identified eight new members of the Golli gene family of transcripts expressed in the human CNS. Golli gene expression was examined by in situ hybridization and immunohistochemistry, and surprisingly, Golli products were found to be expressed in neurons as well as oligodendrocytes. Furthermore, the subcellular distribution of Golli immunoreactivity in fetal spinal cord interneurons shifted between the various laminae. Golli protein was localized within the nuclei of interneurons in the posterior horn, but was found in the cell bodies and processes of interneurons in the anterior horn. Within oligodendrocytes, Golli protein was detected in the cell bodies and processes, including processes which were wrapping axonal segments. Golli mRNA expression was also observed in neurons within the cerebral cortex between 18 and 20 weeks postconception, prior to myelination of this brain region. During this period, there was a striking developmental increase in the numbers and in the locations of neurons expressing Golli mRNAs within the cortical plate. The diverse distribution of Golli proteins within neurons and oligodendrocytes indicates that their function is quite different from that of the MBPs to which they are closely related.

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Cell‐type specific segregation of transcriptional expression of glial genes in the rat peripheral neurotumor RT4 cell lines

Cited by 20 publications

References 57 publications

Glial-specific cAMP response of the glial fibrillary acidic protein gene cell lines.

Glial-specific cAMP response of the glial fibrillary acidic protein gene cell lines.

Expression of the Brain Creatine Kinase Gene in Rat RT4 Peripheral Neurotumor Cell Lines and Its Modulation by Cell Confluence

Expression of the myelin basic protein gene locus in neurons and oligodendrocytes in the human fetal central nervous system

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