Glycine Protects Hepatocytes from Injury Caused by Anoxia, Cold Ischemia and Mitochondrial Inhibitors, But Not Injury Caused by Calcium Ionophores or Oxidative Stress

Abstract

Isolated hepatocytes, suspended in an organ preservation solution, can be preserved at 4 degrees C for up to 6 days. After preservation, normothermic-normoxic incubation causes loss of hepatocyte viability. The addition of 3 mmol/L glycine to the rewarming medium prevents the loss of viability. In this study we investigated the cytoprotective effects of glycine under many conditions known to cause hepatocellular injury to understand the mechanism of cold-induced injury in the liver. Hepatocytes were suspended in modified Krebs-Henseleit buffer with or without 3 mmol/L glycine and exposed to agents or conditions known to induce cell death. Hepatocyte viability was assessed by measuring the percentage of lactate dehydrogenase leakage from the cells and the concentration of ATP during incubation at 37 degrees C under room air for up to 90 min. Mitochondrial inhibitors (potassium cyanide and carbonyl cyanide m-chlorophenylhydrazone); calcium ionophores (ionomycin and A23187); an oxidizing agent, tert-butyl hydroperoxide; and anoxia were all used to cause cell injury. Hepatocytes were also isolated from fasted rats and hypothermically preserved as another model of cell death. Other amino acids were also tested in the hypothermic preservation model to study the specificity of the amino acid requirement for prevention of lactate dehydrogenase leakage. Of the amino acids tested, only alanine (10 mmol/L) and the combination of alanine (3 mmol/L) and serine (3 mmol/L) were as effective as glycine in preventing lactate dehydrogenase release in the hypothermic preservation model.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry

“…These metabolites were mainly increased 3-hydroxybutyric acid (BHBA) and nonesterified fatty acids (NEFAs), including palmitic acid (PA), heptadecanoic acid (HA), stearic acid (SA), trans-9-octadecenoic acid (T-9-OA), myristic acid (MA), cis-9-hexadecenoic acid (C-9-HA), which belong to the families of ketone bodies, long chain unsaturated fatty acids, and saturated acids [1,26], confirming that a great amount of fat mobilization resulting from hypoglycemia may cause ketosis. In addition, some up-regulated amino acids and their catabolic products, such as L-ile, a glucogenic and ketogenic amino acid [25]; Gly, biosynthesized from serine [27]; AMA, a constituent of proteins before hydrolysis [28]; and 2-piperidinecarboxylic acid (2PC), a metabolite of the lysine metabolism [29]; suggest that proteolysis increases to meet body energy demand in both CK and SK. Since 2PC up-regulation was highest in both CK and SK, it may play an important role in ketone body synthesis as a catabolic product of ketogenic lysine [29].…”

Immunomodulatory effects of glycine on LPS‐treated monocytes: reduced TNF‐α production and accelerated IL‐10 expression

“…This effect was reversed by strychnine, leading to the conclusion that Kupffer cells contain a GLY-gated chloride channel. These studies delivered the pathophysiological explanation of earlier findings, in which GLY has been shown to be protective against hypoxia and ischemia in hepatocytes in a low-flow perfusion model and against various cytotoxic substances in renal tubules (22)(23)(24)(25). Moreover, GLY has been shown to be a useful additive to organ preservation solutions: it improves graft function, increases survival after rat liver transplantion, and reduces the nephrotoxicity of cyclosporine by interfering with oxygen radical metabolism (26).…”

Streptococcus pyogenesinduces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway

“…This suggests that the protective effect of glycine was not due to simple osmoprotection but rather to a specific activity of this amino acid. The remarkable property of glycine protection against cell killing has been demonstrated in a variety of other cell types (Weinberg et al, 1987;Marsh et al, 1993;Nishimura et al, 1998). Glycine blocks opening of organic anion channels that are permeable to chloride and polyvalent anions (Nishimura and Lemasters, 2001;Zhong et al, 2003).…”