Branched-chain amino acids inhibit the TGF-beta-induced down-regulation of taurine biosynthetic enzyme cysteine dioxygenase in HepG2 cells.

Taurine deficiency has been suggested to contribute to the pathogenesis and complications of advanced hepatic diseases. The molecular basis for a low level of taurine associated with hepatic failure is largely unknown. Using carbon tetrachloride (CCl4)-induced cirrhotic rat model, we found that the activity and expression of cysteine dioxygenase (CDO), a rate-limiting enzyme in taurine synthesis, were significantly decreased in the liver of these rats.

Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells.

Objective: The elemental diet is one of the effective therapies for inflammatory bowel disease. However, the mechanism remains unclear, and there have never been reports about the inhibitory effects of amino acids in human monocytes/macrophages. We investigated the inhibitory effects of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases, in human monocytes/macrophages.

Redox state of albumin is not associated with colloid osmotic pressure.

Serum albumin exists in oxidized and reduced forms. Although the oxidation of albumin affects some of its functions, the relationship between oxidized albumin and colloid osmotic pressure (COP) remains unclear. The aim of this study was to determine whether there is an association between oxidized albumin and COP.

Localization of polypyrimidine-tract-binding protein is involved in the regulation of albumin synthesis by branched-chain amino acids in HepG2 cells.

Long-term supplementation of branched-chain amino acids (BCAA) improves hypoalbuminemia in patients with cirrhosis. Our previous findings have suggested that the binding of polypyrimidine-tract-binding protein (PTB) to rat albumin mRNA attenuates its translation. The aim of the present study was to investigate the role of PTB in the regulation of albumin synthesis by BCAA in human hepatoma cells.

Identification and characterization of oxidized human serum albumin. A slight structural change impairs its ligand-binding and antioxidant functions.

Human serum albumin (HSA) exists in both reduced and oxidized forms, and the percentage of oxidized albumin increases in several diseases. However, little is known regarding the pathophysiological significance of oxidation due to poor characterization of the precise structural and functional properties of oxidized HSA. Here, we characterize both the structural and functional differences between reduced and oxidized HSA.

An elemental diet controls inflammation in indomethacin-induced small bowel disease in rats: the role of low dietary fat and the elimination of dietary proteins.

Elemental diets (EDs) are effective in treating Crohn's disease. We hypothesize that low dietary fat and amino acids used as the sole nitrogen source are the major contributors for the success of EDs. We examined the influences of the addition of dietary fat and protein to an ED using an indomethacin-induced inflammation model in rat small intestine.

Oral administration of branched-chain amino acids activates the mTOR signal in cirrhotic rat liver.

BCAA granules (a mixture of branched-chain amino acids) have been used to reverse the hypoalbuminemia of decompensated liver cirrhotic patients in Japan. Our previous studies showed that BCAA promoted albumin secretion through the mTOR signal transduction pathway in rat primary hepatocyte culture [Ijichi C, Matsumura T, Tsuji T, Eto Y. Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system.

Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis.

It is well established that impaired glucose metabolism is a frequent complication in patients with hepatic cirrhosis. We previously showed that leucine, one of the branched-chain amino acids (BCAA), promotes glucose uptake under insulin-free conditions in isolated skeletal muscle from normal rats. The aim of the present study was to evaluate the effects of BCAA on glucose metabolism in a rat model of CCl(4)-induced cirrhosis (CCl(4) rats).

The glycine analogue, aminomethanesulfonic acid, inhibits LPS-induced production of TNF-alpha in isolated rat Kupffer cells and exerts hepatoprotective effects in mice.

The activation of Kupffer cells represents a central mechanism of liver injury involving the production of TNF-alpha. It is known that glycine prevents LPS-induced production of TNF-alpha in isolated Kupffer cells. In this study, the possibility that glycine analogues might affect Kupffer cells was investigated.

Pharmacological activities of branched-chain amino acids: specificity of tissue and signal transduction.

Branched-chain amino acid (BCAA: Leu, Ile, and Val) mixture has been used for treatment of hypoalbuminemia in patients with decompensated liver cirrhosis in Japan. It has been known that BCAA, especially leucine, activates mTOR signals and inhibition of protein degradation results in promoting protein synthesis in vitro. Furthermore, leucine activates glycogen synthase via mTOR signals in L6 cell, but not hepatocyte, and it has been shown that leucine improved glucose metabolism in normal and cirrhosis model rats.

L-cysteine administration prevents liver fibrosis by suppressing hepatic stellate cell proliferation and activation.

Recent studies showed that the function of some amino acids is not only nutritional but also pharmacological. However, the effects of amino acids on liver fibrosis and hepatic stellate cell (HSC) remain unclear. In this research, as a result of screening of amino acids using liver fibrosis induced by DMN administration, L-cysteine was selected as a suppressor of liver fibrosis.

Leucine promotes glucose uptake in skeletal muscles of rats.

Soleus muscles isolated from normal rats were incubated to evaluate whether or not leucine promotes glucose uptake under insulin-free conditions, using a labeled 2-deoxyglucose uptake assay. Glucose uptake was promoted by 2mM leucine. A metabolite of leucine, alpha-ketoisocaproic acid (alpha-KIC), also exhibited a similar stimulatory effect, although this was not as potent as leucine.

Mechanisms of the protective effect of L-alanine to D-galactosamine-induced hepatocellular injury: comparative studies of L-alanine and pyruvate.

The addition of L-alanine reduced lactate dehydrogenase leakage from primary cultured rat hepatocytes treated with galactosamine (D-gal), while D-alanine and other amino acids did not. However, the mechanisms have not yet been entirely clarified. In this study, we used various inhibitors of metabolism, i.