Glycine cytoprotection during lethal hepatocellular injury from adenosine triphosphate depletion

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Glycine protects renal tubule cells from cell death during adenosine triphosphate (ATP) depletion. Although the liver plays a key role in glycine metabolism, information is lacking regarding the effects of glycine on lethal hepatocellular injury. Thus, the aim of this study was to determine the potential cytoprotective role of glycine during ATP depletion of rat hepatocytes. Metabolic inhibition with 2.5 mmol/L potassium cyanide (KCN) was used to produce ATP depletion. Hepatocyte suspensions treated with KCN had a 2-hour viability of 5.9% ± 2.0%, whereas cells treated with KCN in the presence of 2.0 mmol/L glycine had a viability of 80.2% ± 1.5%, which was virtually identical to controls (81.5% ± 1.9%). Glycine cytoprotection was dose dependent and amino acid specific. The cytoprotective effect of glycine was not mediated by protein synthesis, glycine mitochondrial metabolism, cytosolic acidosis, or preservation of either intracellular cellular glutathione or ATP. However, glycine did decrease total cellular proteolysis by 18% ± 2%, 25% ± 3%, and 33% ± 1% after 1, 2, and 3 hours of KCN treatment, respectively (P < 0.01). Inhibition of proteolysis by glycine was dose dependent over the same range as its cytoprotection. The results suggest that glycine protects against hepatocellular injury by inhibiting degradative proteolytic activity. It was concluded that proteolysis may be an important mechanism contributing to lethal injury of hepatocytes during ATP depletion.

Original languageEnglish (US)
Pages (from-to)2098-2107
Number of pages10
JournalGastroenterology
Volume102
Issue number6
DOIs
StatePublished - Jun 1992

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Glycine cytoprotection during lethal hepatocellular injury from adenosine triphosphate depletion'. Together they form a unique fingerprint.

Cite this