Low dietary inorganic phosphate affects the brain by controlling apoptosis, cell cycle and protein translation.
Inorganic phosphate (Pi) plays a key role in diverse physiologic functions. In a previous study, we showed that high dietary Pi perturbs brain growth through Akt/ERK signaling in developing mice. However, no study has investigated the response of the brain to low dietary Pi. In this study, we addressed this question by studying the effects of low dietary Pi on the cerebrum of developing mice. Two-week-old weaned mice were fed with a low phosphate diet for 4 weeks. At the end of the study, their cerebrum was dissected and signals important for protein translation, apoptosis and cell cycle were examined. The low phosphate diet did not cause physiologically significant changes; it increased the protein expression of phosphatase and tensin homolog deleted on chromosome 10 but decreased Akt activity. In addition, expression of eukaryotic translation initiation factor binding protein coupled with increased complex formation of eukaryotic translation initiation factor 4E/eukaryotic translation initiation factor binding protein 1 was induced in the cerebrum by low phosphate, leading to reduced cap-dependent protein translation. Finally, low phosphate facilitated apoptosis and suppressed signals important for the cell cycle in the cerebrum of dual-luciferase reporter mice. In summary, our results showed that a low phosphate diet affects the brain by controlling protein translation, apoptosis and cell cycle in developing mice. Our results support the hypothesis that Pi works as a stimulus capable of increasing or decreasing several pivotal genes for normal development and suggest that regulation of Pi consumption is important in maintaining a healthy life.
Jin
Hua
H
Laboratory of Toxicology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
Hwang
Soon-Kyung
SK
Kwon
Jung-Taek
JT
Lee
Yeon-Sook
YS
An
Gil-Hwan
GH
Lee
Kee-Ho
KH
Prats
Anne-Catherine
AC
Morello
Dominique
D
Beck
George R
GR
Cho
Myung-Haing
MH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D002453:Cell Cycle / Q000502:physiology*; D004032:Diet; D018507:Gene Expression Regulation, Developmental; D049409:Luciferases, Firefly / Q000235:genetics; D049410:Luciferases, Renilla / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010710:Phosphates / Q000008:administration & dosage* / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000032:analysis
D010710:Phosphates; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D049410:Luciferases, Renilla; D049409:Luciferases, Firefly; D051057:Proto-Oncogene Proteins c-akt