Effects of dietary protein on the induction of DNA synthesis and expression of growth-related genes in liver and kidney of growing rats.
To investigate molecular mechanisms of growth control by protein nutrition, we examined whether nutritive quality of protein affects the induction of DNA synthesis in liver and kidney of growing rats in relation to expression of growth-related genes such as c-myc, c-fos, c-Ha-ras, and ornithine decarboxylase (ODC). Rats were adapted to 2-h meal feeding schedule at first with laboratory chow for 10 days and then with a protein-free diet for 3 days prior to experiments. When protein-free diet was fed to the rats, the levels of c-myc, ODC and c-Ha-ras mRNAs increased in the liver within 2 days. However, substantial changes in the levels of those mRNAs were not observed in the kidney. The level of c-fos mRNA in these tissues was too low to detect by our method. Feeding of casein diet to rats that had been maintained on protein-free diet for 3 days caused a rapid decrease in the level of c-myc mRNA and induced DNA synthesis in the liver. On the other hand, zein diet, which lacks tryptophan and lysine, did not lower the c-myc mRNA level nor induced DNA synthesis in the liver. However, if zein diet was supplemented with tryptophan and lysine, a decrease in c-myc mRNA level and an induction of DNA synthesis were observed. The levels of ODC and c-Ha-ras mRNAs were not changed by feeding of casein or zein diet. Neither casein nor zein induced DNA synthesis and changed the levels of the mRNA in the kidney. The amount of food intake during the 2-h feeding period was not different among the diets. These results suggest that the liver cells are arrested in G1 phase during the feeding of protein-free diet and good quality of protein is required to progress the cell cycle to enter S phase.
Yokota
T
T
Department of Nutrition, Jikei University School of Medicine, Tokyo, Japan.
Kanamoto
R
R
Hayashi
S
S
D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology; D004247:DNA / Q000096:biosynthesis*; D004044:Dietary Proteins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D008239:Lysine / Q000494:pharmacology; D008297:Male; D015689:Oncogene Protein p21(ras) / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000494:pharmacology
D002364:Caseins; D004044:Dietary Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014364:Tryptophan; D004247:DNA; D015689:Oncogene Protein p21(ras); D009955:Ornithine Decarboxylase; D008239:Lysine