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Regulation of retinoid receptors by retinoic acid and axonal contact in Schwann cells.

Latasa MJ, Cosgaya JM - PLoS ONE (2011)

Bottom Line: As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type.The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability.All together, our results show that retinoid receptors are regulated in a complex manner in Schwann cells, suggesting that they could have a prominent role as regulators of Schwann cell physiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.

ABSTRACT

Background: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type.

Methodology/principal findings: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-γ depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-γ mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-β mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without changes in mRNA stability.

Conclusions/significance: All together, our results show that retinoid receptors are regulated in a complex manner in Schwann cells, suggesting that they could have a prominent role as regulators of Schwann cell physiology.

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Related in: MedlinePlus

RXR-γ expression is increased in DRGN/SC cocultures.(A) The mRNA levels of all six RARs and RXRs were analyzed by Q-RT-PCR. The results are shown as the mean value ± SD relative to the levels found in whole adult rat brain (dashed line). (B) The mRNA levels of RAR-β and RXR-γ were analyzed by Q-RT-PCR in isolated SCs or myelination-competent DRGN/SC cocultures and compared to isolated DRG neurons and total adult rat brain. The results are shown as the mean value ± SEM relative to the levels found in isolated SCs.
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pone-0017023-g001: RXR-γ expression is increased in DRGN/SC cocultures.(A) The mRNA levels of all six RARs and RXRs were analyzed by Q-RT-PCR. The results are shown as the mean value ± SD relative to the levels found in whole adult rat brain (dashed line). (B) The mRNA levels of RAR-β and RXR-γ were analyzed by Q-RT-PCR in isolated SCs or myelination-competent DRGN/SC cocultures and compared to isolated DRG neurons and total adult rat brain. The results are shown as the mean value ± SEM relative to the levels found in isolated SCs.

Mentions: We have recently shown that retinoic acid regulates myelin formation in the peripheral nervous system. In order to analyze which receptors were present in SCs, we performed real time RT-Q-PCR from primary Schwann cell cultures compared to primary DRG sensory neurons and total brain. In general, with the exception of RAR-β, all retinoid receptors, RARs and RXRs, were expressed by isolated Schwann cells at levels comparable or superior to DRG sensory neurons or total brain, which is known to express all retinoid receptors at relatively high levels (Fig. 1A).


Regulation of retinoid receptors by retinoic acid and axonal contact in Schwann cells.

Latasa MJ, Cosgaya JM - PLoS ONE (2011)

RXR-γ expression is increased in DRGN/SC cocultures.(A) The mRNA levels of all six RARs and RXRs were analyzed by Q-RT-PCR. The results are shown as the mean value ± SD relative to the levels found in whole adult rat brain (dashed line). (B) The mRNA levels of RAR-β and RXR-γ were analyzed by Q-RT-PCR in isolated SCs or myelination-competent DRGN/SC cocultures and compared to isolated DRG neurons and total adult rat brain. The results are shown as the mean value ± SEM relative to the levels found in isolated SCs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046125&req=5

pone-0017023-g001: RXR-γ expression is increased in DRGN/SC cocultures.(A) The mRNA levels of all six RARs and RXRs were analyzed by Q-RT-PCR. The results are shown as the mean value ± SD relative to the levels found in whole adult rat brain (dashed line). (B) The mRNA levels of RAR-β and RXR-γ were analyzed by Q-RT-PCR in isolated SCs or myelination-competent DRGN/SC cocultures and compared to isolated DRG neurons and total adult rat brain. The results are shown as the mean value ± SEM relative to the levels found in isolated SCs.
Mentions: We have recently shown that retinoic acid regulates myelin formation in the peripheral nervous system. In order to analyze which receptors were present in SCs, we performed real time RT-Q-PCR from primary Schwann cell cultures compared to primary DRG sensory neurons and total brain. In general, with the exception of RAR-β, all retinoid receptors, RARs and RXRs, were expressed by isolated Schwann cells at levels comparable or superior to DRG sensory neurons or total brain, which is known to express all retinoid receptors at relatively high levels (Fig. 1A).

Bottom Line: As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type.The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability.All together, our results show that retinoid receptors are regulated in a complex manner in Schwann cells, suggesting that they could have a prominent role as regulators of Schwann cell physiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.

ABSTRACT

Background: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type.

Methodology/principal findings: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-γ depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-γ mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-β mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without changes in mRNA stability.

Conclusions/significance: All together, our results show that retinoid receptors are regulated in a complex manner in Schwann cells, suggesting that they could have a prominent role as regulators of Schwann cell physiology.

Show MeSH
Related in: MedlinePlus