Abstract
Down syndrome (DS) patients overexpress human DS critical region gene 1 (hDSCR-1), whose translational product inhibits calcineurin-dependent signaling pathways of genetic transcription. Compared to hDSCR-1, C. elegans rcn-1 has 40% sequence similarity and its proteins share an analogous function with hDSCR-1 in regulating calcineurin. Taurine has had a positive effect on DS patients. According to animal research studies, taurine reduces the expression of MCIP1, a calcineurin inhibitory protein, on C2C12 myotubes and fibroblast in mouse. This study utilizes two C. elegans models for DS: rcn-1 overexpression model, displaying a calcineurin-deficient phenotype, and calcineurin loss-of function mutants. C. elegans larvae were treated with taurine to characterize its effect and mechanism in helping DS patients. RCN-1 expression and behavioral changes were examined in rcn-1 overexpression and calcineurin-deficient models at different concentrations of taurine. When treated with taurine, transgenic worms harboring an rcn-1 reporter (RCN-1::GFP) showed a reduced level of rcn-1 mRNA expression and improved behaviors that were comparable to those in the wild type. These results indicate that taurine exerts a down-regulating effect on the expression of rcn-1 and, consequently, a positive effect on the expression of calcineurins. In summary, taurine may improve the DS symptoms by prompting a positive interaction between RCN-1 and calcineurin. Furthermore, these results suggest that novel mechanisms may regulate interactions among taurine, RCN-1 and calcineurin.
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Abbreviations
- CnA:
-
Calcineurin A
- DS:
-
Down syndrome
- DSCR-1:
-
Down syndrome critical region 1
- GFP:
-
Green fluorescent protein
- GOF:
-
Gain of function
- LOF:
-
Loss of function
- NGM:
-
Nematode growth medium
- RCN:
-
Regulator of calcineurin
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Acknowledgements
This work was supported by the 2015 University of Seoul Faculty Grant to DH Lee. The authors appreciate for the financial support.
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Ko, Y.J., Chang, H., Lee, D.H. (2017). Analysis of Taurine’s Anti-Down Syndrome Potential in Caenorhabditis elegans. In: Lee, DH., Schaffer, S.W., Park, E., Kim, H.W. (eds) Taurine 10. Advances in Experimental Medicine and Biology, vol 975. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1079-2_89
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DOI: https://doi.org/10.1007/978-94-024-1079-2_89
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