Limits...
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.

Show MeSH

Related in: MedlinePlus

Expression of the creatine synthesizing enzymes AGAT and GAMT in the brain during fetal and neonatal development. A, Brain AGAT mRNA expression; B. Brain GAMT mRNA expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. AGAT and GAMT protein could not be detected with western blot, possibly due to low level expression in whole brain homogenates. 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
getmorefigures.php?uid=PMC2713216&req=5

Figure 5: Expression of the creatine synthesizing enzymes AGAT and GAMT in the brain during fetal and neonatal development. A, Brain AGAT mRNA expression; B. Brain GAMT mRNA expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. AGAT and GAMT protein could not be detected with western blot, possibly due to low level expression in whole brain homogenates. 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: AGAT mRNA expression showed a gradual increase between gestational days 20, 25, 30, 34 and 37, although only reached significance between days 20 and 37 (p < .05, Figure 5A). A further 2-fold increase in AGAT mRNA expression occurred by postnatal day 2 (p < .05), and remained unchanged at postnatal day 10. Expression of GAMT mRNA in the fetal brain was relatively low between 20–30 days gestation, with a significant 10-fold increase by 34 days gestation (p < .05, Figure 5B). Levels remained unchanged by 37 days gestation and into the postnatal period. Although mRNA for both AGAT and GAMT were detected, the corresponding proteins could not be detected by Western blot analysis (data not shown).


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 brain during fetal and neonatal development. A, Brain AGAT mRNA expression; B. Brain GAMT mRNA expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. AGAT and GAMT protein could not be detected with western blot, possibly due to low level expression in whole brain homogenates. 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 5: Expression of the creatine synthesizing enzymes AGAT and GAMT in the brain during fetal and neonatal development. A, Brain AGAT mRNA expression; B. Brain GAMT mRNA expression. All mRNA data are normalized to 18S and shown relative to 37 days gestation. AGAT and GAMT protein could not be detected with western blot, possibly due to low level expression in whole brain homogenates. 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: AGAT mRNA expression showed a gradual increase between gestational days 20, 25, 30, 34 and 37, although only reached significance between days 20 and 37 (p < .05, Figure 5A). A further 2-fold increase in AGAT mRNA expression occurred by postnatal day 2 (p < .05), and remained unchanged at postnatal day 10. Expression of GAMT mRNA in the fetal brain was relatively low between 20–30 days gestation, with a significant 10-fold increase by 34 days gestation (p < .05, Figure 5B). Levels remained unchanged by 37 days gestation and into the postnatal period. Although mRNA for both AGAT and GAMT were detected, the corresponding proteins could not be detected by Western blot analysis (data not shown).

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