Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After traumatic injury to the central nervous system (CNS), various cytokines orchestrate the physiological responses of injured neurons and glial cells. The control of these intercellular signals is of major interest from a medical point of view. Since the transcriptional activator retinoic acid (RA) is known to regulate gene expression of cytokines in various cell culture systems we investigated the role of RA signaling in glial cells. The transcriptional activity of RA-induced genes is largely determined by the distribution of RA, which in turn depends on the local oxidation of retinaldehyde (RAL). This is synthesized from retinol or internalized as a component of vitamin A. Using high-pressure liquid chromatography and an RA-sensitive reporter cell line, we showed that OLN-93 cells, which serve as a model system for CNS oligodendrocytes, convert all-trans-RAL to the biologically active form all-trans-RA, but neither oxidize 9-cis-RAL nor isomerize RA enzymatically. The oligodendrocyte cell line expresses a cytosolic aldehyde dehydrogenase with an apparent molecular weight of 54-57 kDa and pI of 5.3-5.7. As indicated by a zymography bioassay, this enzyme is responsible for RA synthesis. The reaction requires NAD+ as cosubstrate and can be inhibited by disulfiram and citral. No other RA-producing enzyme activities were detected. These findings are in accordance with a putative role for retinoid signaling in neuroglial interactions in the CNS.
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PMID:OLN-93 oligodendrocytes synthesize all-trans-retinoic acid in vitro. 1107 15

Brain injuries trigger physiological reactions which are mediated by a number of cytokines including interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF). Astrocytes and microglia, the protagonists in these traumatic responses, are known to secrete a variety of paracrine signals. Oligodendrocytes are involved as well and constitute another possible source of cytokines. Here we show the expression of IL-6, CNTF, and LIF in OLN-93 cells, derived from rat oligodendrocyte primary cultures. While differential gene transcription after injury has been described for many cytokines, the regulation of these physiological responses is unknown in many instances. Recent experiments indicate that the transcriptional activator retinoic acid (RA) plays a role in peripheral nerve regeneration. Transcripts of the retinoic acid receptors and the retinoid X receptors were also detected in OLN-93 oligodendrocytes. Using quantitative RT-PCR, we have therefore investigated the effect of RA on the expression of neuropoietic cytokines in these cells. Treatment with 1 microM all- trans RA for 24 h increased the mRNA concentration of LIF by a factor of 3.1 ( P<0.01). In contrast, RA had no significant effect on the expression of CNTF. The results suggest RA as a possible regulator of cytokine signaling in the CNS.
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PMID:Retinoic acid enhances leukemia inhibitory factor expression in OLN-93 oligodendrocytes. 1239 70