Abstract
Taurine, a sulfur containing amino acid, has various physiological functions including development of the eye and brain, immune function, reproduction, osmo-regulatory function as well as anti-oxidant and anti-inflammatory activities. In order to understand the physiological role, we developed taurine deficient mice deleting a rate-liming enzyme, cysteine sulfinic acid decarboxylase (CSAD) for biosynthesis of taurine. Taurine was measured in various tissues including the liver, brain, lung, spleen, thymus, pancreas, heart, muscle and kidney as well as plasma from CSAD knock-out mice (CSAD KO) with and without treatment of taurine in the drinking water at the age of 2 months (2 M). Taurine was determined using HPLC as a phenylisothiocyanate derivative of taurine at 254 nm. Taurine concentrations in the liver and kidney from homozygotes of CSAD KO (HO), in which CSAD level is high, were 90% and 70% lower than WT, respectively. Taurine concentrations in the brain, spleen and lung, where CSAD level is low, were 21%, 20% and 28% lower than WT, respectively. At 2 M, 1% taurine treatment of HO restored taurine concentrations in all tissues compared to that of WT. To select an appropriate taurine treatment, HO were treated with various concentrations (0.05, 0.2, 1%) of taurine for 4 months (4 M). Restoration of taurine in all tissues except the liver, kidney and lung requires 0.05% taurine to be restored to that of WT. The liver and kidney restore taurine back to WT with 0.2% taurine. To examine which enzymes influence taurine concentrations in various tissues from WT and HO at 2 M, expression of five taurine-related enzymes, two antioxidant enzymes as well as lactoferrin (Lft) and prolactin receptor (Prlr) was determined using RT2 qPCR. The expression of taurine transporter in the liver, brain, muscle and kidney from HO was increased except in the lung. Our data showed expression of glutamate decarboxylase-like 1(Gadl-1) was increased in the brain and muscle in HO, compared to WT, indicating taurine in the brain and muscle from HO was replenished through taurine transporter and increased biosynthesis of taurine by up-regulated Gadl-1. The expression of glutathione peroxidase 3 was increased in the brain and peroxireductase 2 was increased in the liver and lung, suggesting taurine has anti-oxidant activity. In contrast to newborn and 1 month CSAD KO, Ltf and Prlr in the liver from CSAD KO at 2 M were increased more than two times and 52%, respectively, indicating these two proteins may be required for pregnancy of CSAD KO. Ltf in HOT1.0 was restored to WT, while Prlr in HOT1.0 was increased more than HO, explaining improvement of neonatal survival with taurine supplementation.
These data are essential for investigating the role of taurine in development of the brain and eye, immune function, reproduction and glucose tolerance.
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Abbreviations
- 2 M and 4 M:
-
The age of 2 months and 4 months
- ADO:
-
Cysteamine (2-aminoenthanethiol) dioxygenase
- CDO KO:
-
Cyteine dioxygenase knockout mice
- CSAD KO:
-
Cysteine sulfinic acid decarboxylase knockout mice
- CDO:
-
Cysteine dioxygenase
- CSAD:
-
Cysteine sulfinic acid decarboxylase
- Gpx 3:
-
Glutathione peroxidase 3
- HO:
-
Homozygotic mice (CSAD−/−)
- HOT:
-
Homozygotic mice treated with 1% taurine
- HOT0.05, HOT0.2 and HOT1.0:
-
Homozygotic mice treated with 0.05%, 0.2% or 1% taurine, respectively
- Ltf:
-
Lactoferrin
- Prdx 2:
-
Peroxireductase 2
- Prlr:
-
Prolactin receptor
- TauT KO:
-
Taurine transporter knockout mice
- TauT:
-
Taurine transporter
- WT:
-
Wild type (CSAD+/+)
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Acknowledgments
This work was supported by the Office for People with Developmental Disabilities, Albany, NY and Dong A Pharmaceutical Co., LTD, Seoul, Korea. We are thankful to Dr. William Levis and Harry C. Meeker for discussing the research and reviewing this manuscript.
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Park, E., Park, S.Y., Cho, I.S., Kim, B.S., Schuller-Levis, G. (2017). A Novel Cysteine Sulfinic Acid Decarboxylase Knock-Out Mouse: Taurine Distribution in Various Tissues With and Without Taurine Supplementation. 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_37
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DOI: https://doi.org/10.1007/978-94-024-1079-2_37
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