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Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse.

Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R - BMC Dev. Biol. (2009)

Bottom Line: The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA.Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Monash University, Clayton, Australia 3800. zoe.ireland@med.monash.edu.au

ABSTRACT

Background: Creatine synthesis takes place predominately in the kidney and liver via a two-step process involving AGAT (L-arginine:glycine amidinotransferase) and GAMT (guanidinoacetate methyltransferase). Creatine is taken into cells via the creatine transporter (CrT), where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands. Very little is known of the fetal requirement for creatine and how this may change with advancing pregnancy and into the early neonatal period. Using the spiny mouse as a model of human perinatal development, the purpose of the present study was to comprehensively examine the development of the creatine synthesis and transport systems.

Results: The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA. In the fetal brain, mRNA expression of AGAT increased steadily across the second half of pregnancy, although GAMT mRNA expression was relatively low until 34 days gestation (term is 38-39 days). In the fetal kidney and liver, AGAT and GAMT mRNA and protein expression were also relatively low until 34-37 days gestation. Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.

Conclusion: Our results suggest that in the spiny mouse, a species where, like the human, considerable organogenesis occurs before birth, there appears to be a limited capacity for endogenous creatine synthesis until approximately 0.9 of pregnancy. This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth. If these results also apply to the human, premature birth may increase the risk of creatine deficiency.

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Expression of the creatine synthesizing enzymes AGAT and GAMT in the kidney and liver during fetal and neonatal development. A, Kidney AGAT mRNA expression; B, Kidney AGAT protein expression; C, Liver GAMT mRNA expression; D, Liver GAMT protein expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. Data points not sharing the same symbol indicate expression is significantly different to all others (p < .05). Mean ± SE. GA, gestational days; PN, postnatal days.
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Figure 4: Expression of the creatine synthesizing enzymes AGAT and GAMT in the kidney and liver during fetal and neonatal development. A, Kidney AGAT mRNA expression; B, Kidney AGAT protein expression; C, Liver GAMT mRNA expression; D, Liver GAMT protein expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. Data points not sharing the same symbol indicate expression is significantly different to all others (p < .05). Mean ± SE. GA, gestational days; PN, postnatal days.

Mentions: The developmental expression of the two key enzymes involved in creatine synthesis, AGAT and GAMT, were measured in the kidney and liver, respectively, at the mRNA and protein level from mid-gestation until the second postnatal week (Figure 4A–D). Expression of AGAT mRNA in the kidney remained relatively low between 30 and 34 days of gestation, with a significant 33-fold increase in expression by 37 days of gestation (p < .05, Figure 4A). A further increase had occurred by postnatal day 2 (p < .05), with no further change by postnatal day 10. The expression of AGAT protein showed a similar profile; protein levels significantly increased between gestational days 30, 37 and postnatal day 10 (p < .05, Figure 4B).


Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse.

Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R - BMC Dev. Biol. (2009)

Expression of the creatine synthesizing enzymes AGAT and GAMT in the kidney and liver during fetal and neonatal development. A, Kidney AGAT mRNA expression; B, Kidney AGAT protein expression; C, Liver GAMT mRNA expression; D, Liver GAMT protein expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. Data points not sharing the same symbol indicate expression is significantly different to all others (p < .05). Mean ± SE. GA, gestational days; PN, postnatal days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713216&req=5

Figure 4: Expression of the creatine synthesizing enzymes AGAT and GAMT in the kidney and liver during fetal and neonatal development. A, Kidney AGAT mRNA expression; B, Kidney AGAT protein expression; C, Liver GAMT mRNA expression; D, Liver GAMT protein expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. Data points not sharing the same symbol indicate expression is significantly different to all others (p < .05). Mean ± SE. GA, gestational days; PN, postnatal days.
Mentions: The developmental expression of the two key enzymes involved in creatine synthesis, AGAT and GAMT, were measured in the kidney and liver, respectively, at the mRNA and protein level from mid-gestation until the second postnatal week (Figure 4A–D). Expression of AGAT mRNA in the kidney remained relatively low between 30 and 34 days of gestation, with a significant 33-fold increase in expression by 37 days of gestation (p < .05, Figure 4A). A further increase had occurred by postnatal day 2 (p < .05), with no further change by postnatal day 10. The expression of AGAT protein showed a similar profile; protein levels significantly increased between gestational days 30, 37 and postnatal day 10 (p < .05, Figure 4B).

Bottom Line: The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA.Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Monash University, Clayton, Australia 3800. zoe.ireland@med.monash.edu.au

ABSTRACT

Background: Creatine synthesis takes place predominately in the kidney and liver via a two-step process involving AGAT (L-arginine:glycine amidinotransferase) and GAMT (guanidinoacetate methyltransferase). Creatine is taken into cells via the creatine transporter (CrT), where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands. Very little is known of the fetal requirement for creatine and how this may change with advancing pregnancy and into the early neonatal period. Using the spiny mouse as a model of human perinatal development, the purpose of the present study was to comprehensively examine the development of the creatine synthesis and transport systems.

Results: The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA. In the fetal brain, mRNA expression of AGAT increased steadily across the second half of pregnancy, although GAMT mRNA expression was relatively low until 34 days gestation (term is 38-39 days). In the fetal kidney and liver, AGAT and GAMT mRNA and protein expression were also relatively low until 34-37 days gestation. Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.

Conclusion: Our results suggest that in the spiny mouse, a species where, like the human, considerable organogenesis occurs before birth, there appears to be a limited capacity for endogenous creatine synthesis until approximately 0.9 of pregnancy. This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth. If these results also apply to the human, premature birth may increase the risk of creatine deficiency.

Show MeSH
Related in: MedlinePlus