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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

Protein synthesis inhibition abrogates RXR-γ, while increasing RAR-β mRNA steady state mRNA levels.SCs were treated with the axonal mimickers forskolin and BPE for 24 hours in the presence or absence of 10 µg/ml of the protein synthesis inhibitor cycloheximide (CHX), and RXR-γ (A) and RAR-β (B) mRNA levels were determined by Q-RT-PCR. All values are shown as the mean ± SEM relative to their respective controls in the absence of cycloheximide.
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pone-0017023-g003: Protein synthesis inhibition abrogates RXR-γ, while increasing RAR-β mRNA steady state mRNA levels.SCs were treated with the axonal mimickers forskolin and BPE for 24 hours in the presence or absence of 10 µg/ml of the protein synthesis inhibitor cycloheximide (CHX), and RXR-γ (A) and RAR-β (B) mRNA levels were determined by Q-RT-PCR. All values are shown as the mean ± SEM relative to their respective controls in the absence of cycloheximide.

Mentions: Next, we analyzed whether de novo protein synthesis was required for RXR-γ induction by axonal contact mimickers. Interestingly, the presence of the protein synthesis inhibitor ciycloheximide produced an almost complete suppression of RXR-γ steady state mRNA levels (Fig. 3A), which could not be reverted by the addition of BPE and forskolin. This result suggests that SCs express a labile inducer, whose continuous presence is required for maintenance of RXR-γ mRNA levels. On the other hand, RAR-β mRNA steady-state levels were increased in the absence of new protein synthesis, while the small reduction achieved by the combined treatment with BPE and forskolin was still visible although at a lesser extent (Fig. 3B).


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

Latasa MJ, Cosgaya JM - PLoS ONE (2011)

Protein synthesis inhibition abrogates RXR-γ, while increasing RAR-β mRNA steady state mRNA levels.SCs were treated with the axonal mimickers forskolin and BPE for 24 hours in the presence or absence of 10 µg/ml of the protein synthesis inhibitor cycloheximide (CHX), and RXR-γ (A) and RAR-β (B) mRNA levels were determined by Q-RT-PCR. All values are shown as the mean ± SEM relative to their respective controls in the absence of cycloheximide.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017023-g003: Protein synthesis inhibition abrogates RXR-γ, while increasing RAR-β mRNA steady state mRNA levels.SCs were treated with the axonal mimickers forskolin and BPE for 24 hours in the presence or absence of 10 µg/ml of the protein synthesis inhibitor cycloheximide (CHX), and RXR-γ (A) and RAR-β (B) mRNA levels were determined by Q-RT-PCR. All values are shown as the mean ± SEM relative to their respective controls in the absence of cycloheximide.
Mentions: Next, we analyzed whether de novo protein synthesis was required for RXR-γ induction by axonal contact mimickers. Interestingly, the presence of the protein synthesis inhibitor ciycloheximide produced an almost complete suppression of RXR-γ steady state mRNA levels (Fig. 3A), which could not be reverted by the addition of BPE and forskolin. This result suggests that SCs express a labile inducer, whose continuous presence is required for maintenance of RXR-γ mRNA levels. On the other hand, RAR-β mRNA steady-state levels were increased in the absence of new protein synthesis, while the small reduction achieved by the combined treatment with BPE and forskolin was still visible although at a lesser extent (Fig. 3B).

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