OCT-4 transcription factors play an important role in maintaining the pluripotent state of embryonic stem cells and may prevent expression of genes activated during differentiation. Human OCT-4 isoform mRNAs encode proteins that have identical POU DNA binding domains and C-terminal domains but differ in their N-terminal domains. We report here the cloning and characterization of the human OCT-4B isoform. Human OCT-4B cDNA encodes a 265-amino acid protein with a predicted molecular mass of 30 kDa. Embryonic stem (ES) cellbased complementation assays using ZHBTc4 ES cells showed that unlike human OCT-4A, OCT-4B cannot sustain ES cell self-renewal. In addition, OCT-4B does not bind to a probe carrying the OCT-4 consensus binding sequence, and we demonstrate that two separate regions of its N-terminal domain are responsible for inhibiting DNA binding. We also demonstrate that OCT-4B is mainly localized to the cytoplasm. Overexpression of OCT-4B did not activate transcription from OCT-4-dependent promoters, although OCT-4A did as reported previously. Furthermore, transcriptional activation by human OCT-4A was not inhibited by co-expression of OCT-4B. Taken together, these data suggest that the DNA binding, transactivation, and abilities to confer self-renewal of the human OCT-4 isoforms differ.
Chronic excess of GH is known to cause hyperinsulinemia and insulin resistance. We developed human GH transgenic (TG) rats, which were characterized by high plasma levels of human GH and IGF-I. These TG rats showed higher levels of plasma insulin, compared with control littermates, whereas plasma glucose concentrations were normal. Insulin-dependent glucose uptake into adipocytes and muscle was impaired, suggesting that these rats developed insulin resistance. In contrast, insulin-independent glucose uptake into hepatocytes from TG rats was significantly increased, and glycogen and lipid levels in livers of TG rats were remarkably high. Because the role of liver in GH-induced insulin resistance is poorly understood, we studied insulin signaling at early stages and insulin action in liver and primary cultures of hepatocytes prepared from TG rats. There was no difference in insulin receptor kinase activity induced by insulin between TG and control rats; however, insulin-dependent insulin receptor substrate-2 tyrosine phosphorylation, glycogen synthase activation, and expression of enzymes that induce lipid synthesis were potentiated in hepatocytes of TG rats. These results suggest that impairment of insulin-dependent glucose uptake by GH excess in adipose tissue and muscle is compensated by up-regulation of glucose uptake in liver and that potentiation of insulin signaling through insulin receptor substrate-2 in liver experiencing GH excess causes an increase in glycogen and lipid synthesis from incorporated glucose, resulting in accumulation of glycogen and lipids in liver. This novel mechanism explains normalization of plasma glucose levels at least in part in a GH excess model.
The self-renewal of hESC is probably maintained by coordinated regulation of signalling-specific molecules and in a signalling-specific manner.
ABSTRACT. The physiological significance of taurine in milk in the growth of rat pups was investigated. Our results confirmed that taurine was at an exceptionally high concentration in rat milk during the lactational period, especially for the first few days after birth. Pups taking no milk from natural dams but from foster mothers at an advanced lactational period showed a slower growth rate. Intraperitoneal administration of taurine to the foster mothers in the first five days restored this growth retardation. On the other hand, intraperitoneal administration of β-alanine, a transport antagonist of taurine, to the natural dams through the lactational period induced a slower growth rate of pups. This β-alanine treatment to dams increased β-alanine concentration, but did not decrease taurine concentrations in milk, and serum taurine concentration in the pups receiving this milk was elevated. Direct administration of β-alanine to pups also increased the serum taurine concentrations dose-dependently. β-Alanine administration to pups significantly decreased [ 3 H]taurine incorporation into all the organs examined, and in contrast, [ 3 H]taurine concentrations in serum and urine were elevated. Thus, β-alanine inhibited taurine incorporation into cells and accelerated taurine excretion into either urine or milk. Serum IGF-I levels in pups receiving β-alanine either directly or via their mothers was significantly lower than those in control pups. Cumulatively, taurine ingestion from milk at an early lactational period seems critical for normal growth of rat neonates due to its role in maintaining normal serum IGF-I levels.KEY WORDS: β-alanine, growth rate, milk, rat pup, taurine.J. Vet. Med. Sci. 62 (7): [693][694][695][696][697][698] 2000 Taurine (2-aminoethane sulphonic acid) is one of the end products of sulfur metabolism, first isolated from ox bile [29], and was considered for a long time to be an inert waste product of the sulfur-containing amino acid catabolism. However, as information concerning the biological roles of taurine has accumulated, taurine has been illustrated to play many important physiological roles in animals, especially during their development. The possible functions of taurine currently proposed are as follows: conjugation of bile acids in the liver [31], improvement of fat absorption [1], maintenance of osmolarity [17], modulation of calcium levels [30], stabilization of membranes [12], antiarrhythmic activity in the heart [24], regulation of ion fluxes [7], and stimulation of sperm motility [20]. In the central nervous system, although the role of taurine is not well established, it has been proposed as a neurotransmitter or a neuromodulator [2]. In addition, taurine seems to be involved in the development of the brain, since taurine concentrations in the brain fall with development and the levels of taurine in adults is about one-third of those of neonates. This pattern has been found in many species including rats [5].Taurine is an essential amino acid for the cat because the cat has ...
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