Decreased hepatic ALT synthesis is an outcome of subchronic microcystin- LR toxicity

Philip F Solter, Zonglin Liu, Roberto Guzman

Research output: Contribution to journalArticlepeer-review

Abstract

Alanine aminotransferase (ALT; EC 2.6.1.2) is important for the transamination of amino acids and is also an important serum marker of hepatic damage. However, we had previously shown that hepatic ALT activity decreases with subchronic exposure to the hepatotoxin, microcystin-LR (MCLR), a potent inhibitor of serine/threonine protein phosphatases types 1 and 2A. These previous findings suggest that one outcome of subchronic MCLR toxicosis is decreased ALT synthesis by hepatocytes. This could affect the diagnostic sensitivity of serum ALT activity and metabolic processes within the cell. This study was done to investigate the mechanism by which ALT activity decreases following prolonged MCLR exposure. Immunoblots were first performed on liver tissue from 12 Harlan-Sprague-Dawley rats that had been treated with 0, 16, 32, or 48 μg/kg of microcystin-LR per day by continuous intraperitoneal infusion for 28 days. These revealed a dose-dependent decrease in ALT protein concentrations that correlated directly with hepatic ALT activity (r = 0.8132; P = 0.0013). Sixteen additional rats, treated with the same doses of MCLR showed a dose-dependent decrease in hepatic ALT activity to approximately 19% of values in saline-treated controls. Northern blot analysis revealed a decrease in hepatic ALT mRNA that correlated directly to hepatic ALT activity (r = 0.7909; P = 0.0004). It was concluded that subchronic MCLR exposure causes decreased hepatic ALT protein and mRNA concentrations. These findings suggest that one sequela of MCLR toxicosis is decreased hepatic ALT synthesis. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)216-220
Number of pages5
JournalToxicology and Applied Pharmacology
Volume164
Issue number2
DOIs
StatePublished - Apr 15 2000

Keywords

  • Alanine aminotransferase
  • Liver
  • Microcystin-LR
  • Protein phosphatase
  • Protein synthesis

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Decreased hepatic ALT synthesis is an outcome of subchronic microcystin- LR toxicity'. Together they form a unique fingerprint.

Cite this