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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

RA upregulates RAR-β and downregulates RXR-γ in myelinating cocultures.(A) DRGN/SC cocultures were allowed to myelinate for 7 days in the presence or absence of 1 µM RA, and the relative levels of RAR-α, -β and -γ, as well as RXR-α, -β and -γ were determined by Q-RT-PCR. All values are shown as the mean ± SD relative to their respective controls (sister cultures treated only with vehicle). (B) Myelinating cocultures were treated with 1 µM RA from the time of ascorbic acid induction and the levels of all six retinoid receptors were determined by Q-RTR-PCR at different times of treatment. All values are shown as the mean ± SD relative to their respective controls (myelinating cocultures treated only with vehicle for the same length of time).
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pone-0017023-g004: RA upregulates RAR-β and downregulates RXR-γ in myelinating cocultures.(A) DRGN/SC cocultures were allowed to myelinate for 7 days in the presence or absence of 1 µM RA, and the relative levels of RAR-α, -β and -γ, as well as RXR-α, -β and -γ were determined by Q-RT-PCR. All values are shown as the mean ± SD relative to their respective controls (sister cultures treated only with vehicle). (B) Myelinating cocultures were treated with 1 µM RA from the time of ascorbic acid induction and the levels of all six retinoid receptors were determined by Q-RTR-PCR at different times of treatment. All values are shown as the mean ± SD relative to their respective controls (myelinating cocultures treated only with vehicle for the same length of time).

Mentions: Retinoic acid treatment produced a tremendous increase in RAR-β mRNA levels without affecting RAR-α or -γ mRNA levels in myelinating Schwann cell/sensory neurons cocultures (Fig. 4A). On the other hand, the retinoid produced a small but reproducible decrease in RXR-α and -β levels, at the same time that RXR-γ mRNA was highly down-regulated. This effect could already be seen after 4 days of treatment, a time point in which active myelin formation is taking place, as well as after 10 days of treatment in which myelin formation in control cocultures has already taken place almost completely (Fig. 4B).


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

Latasa MJ, Cosgaya JM - PLoS ONE (2011)

RA upregulates RAR-β and downregulates RXR-γ in myelinating cocultures.(A) DRGN/SC cocultures were allowed to myelinate for 7 days in the presence or absence of 1 µM RA, and the relative levels of RAR-α, -β and -γ, as well as RXR-α, -β and -γ were determined by Q-RT-PCR. All values are shown as the mean ± SD relative to their respective controls (sister cultures treated only with vehicle). (B) Myelinating cocultures were treated with 1 µM RA from the time of ascorbic acid induction and the levels of all six retinoid receptors were determined by Q-RTR-PCR at different times of treatment. All values are shown as the mean ± SD relative to their respective controls (myelinating cocultures treated only with vehicle for the same length of time).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017023-g004: RA upregulates RAR-β and downregulates RXR-γ in myelinating cocultures.(A) DRGN/SC cocultures were allowed to myelinate for 7 days in the presence or absence of 1 µM RA, and the relative levels of RAR-α, -β and -γ, as well as RXR-α, -β and -γ were determined by Q-RT-PCR. All values are shown as the mean ± SD relative to their respective controls (sister cultures treated only with vehicle). (B) Myelinating cocultures were treated with 1 µM RA from the time of ascorbic acid induction and the levels of all six retinoid receptors were determined by Q-RTR-PCR at different times of treatment. All values are shown as the mean ± SD relative to their respective controls (myelinating cocultures treated only with vehicle for the same length of time).
Mentions: Retinoic acid treatment produced a tremendous increase in RAR-β mRNA levels without affecting RAR-α or -γ mRNA levels in myelinating Schwann cell/sensory neurons cocultures (Fig. 4A). On the other hand, the retinoid produced a small but reproducible decrease in RXR-α and -β levels, at the same time that RXR-γ mRNA was highly down-regulated. This effect could already be seen after 4 days of treatment, a time point in which active myelin formation is taking place, as well as after 10 days of treatment in which myelin formation in control cocultures has already taken place almost completely (Fig. 4B).

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