Creatine transporter (SLC6A8) knock out mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle
| Autor: | Séverine Lamon, Craig R. Wright, Matthew R. Skelton, Rodney J. Snow, Erin L. Brown, Aaron P. Russell, Lobna Ghobrial, Michihiro Kon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
genetic structures Physiology Transgene Biology Creatine lcsh:Physiology Gastrocnemius muscle chemistry.chemical_compound Physiology (medical) Internal medicine Gene expression medicine Original Research Article skeletal muscle creatine synthesis transgenic lcsh:QP1-981 Wild type Skeletal muscle Guanidinoacetate N-methyltransferase Endocrinology medicine.anatomical_structure chemistry Knockout mouse Creatine transporter Energy Metabolism |
| Zdroj: | Frontiers in Physiology, Vol 5 (2014) Frontiers in Physiology |
| DOI: | 10.3389/fphys.2014.00314/full |
| Popis: | The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT(-/y)) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT(-/y) and wild type (CrT(+/y)) mice were analyzed for ATP, Cr, Cr phosphate (CrP), and total Cr (TCr) content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine amidotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) were also determined as were the rates of in vitro Cr biosynthesis. CrT(-/y) mice muscle contained measurable (22.3 ± 4.3 mmol.kg(-1) dry mass), but markedly reduced (P0.05) TCr levels compared with CrT(+/y) mice (125.0 ± 3.3 mmol.kg(-1) dry mass). AGAT gene and protein expression were higher (~3 fold; P0.05) in CrT(-/y) mice muscle, however GAMT gene and protein expression remained unchanged. The in vitro rate of Cr biosynthesis was elevated 1.5 fold (P0.05) in CrT(-/y) mice muscle. These data clearly demonstrate that in the absence of CrT protein, skeletal muscle has reduced, but not absent, levels of Cr. This presence of Cr may be at least partly due to an up regulation of muscle Cr biosynthesis as evidenced by an increased AGAT protein expression and in vitro Cr biosynthesis rates in CrT(-/y) mice. Of note, the up regulation of Cr biosynthesis in CrT(-/y) mice muscle was unable to fully restore Cr levels to that found in wild type muscle. |
| Databáze: | OpenAIRE |
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