Homocysteine modifies extracellular ATP availability in macrophages.

Abstract

Increased levels of plasma homocysteine (hyperhomocysteinemia-HHcy) are associated to the development of coronary artery disease (CAD), peripheral vascular disease and thrombosis. In addition, recent studies have shown that inflammation, probably mediated by macrophages, mediates the pathogenesis associated to high levels of homocysteine (Hcy). In the present study, we evaluated the Hcy effects in the ATP hydrolysis and its breakdown products in murine macrophages. The results showed that micromolar concentrations of Hcy increased the ATP, ADP and AMP hydrolysis. Additionally, our results show decreased inosine levels in the extracellular milieu of Hcy-exposed macrophages. The increasing in ATP, ADP and AMP hydrolysis are not explained by increased transcription or protein expression of NTPDases and ecto-5'-nucleotidase (ecto-5'-NT/CD73) enzymes. Moreover, the formation of reactive oxygen species did not interfere in the Hcy effects, which suggest that Hcy or Hcy metabolites act directly on the modulation of NTPDases and ecto-5'-NT/CD73 activities. In conclusion, Hcy induces the rapid breakdown of ATP, ADP and AMP to adenosine (ADO), which is classically known as an anti-inflammatory response in immune cells. However, by the action of these enzymes, the extracellular adenosine generated during Hcy treatment probably is uptaken into the cells, as evidenced by the decreased in inosine formation, and thus collaborating to the inflammatory complications associates to HHcy.

• Authors: Rafael Fernandes Zanin, Letícia Scussel Bergamin, Elizandra Braganhol, Jean Sévigny, Angela Terezinha de Souza Wyse, Ana Maria Oliveira Battastini
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 27 Issue 8 Pg. 2273-8 (Dec 2013) ISSN: 1879-3177 [Electronic] England
• PMID: 24055814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• RNA, Messenger
• Receptors, Purinergic P1
• Receptors, Purinergic P2
• Homocysteine
• Adenosine Triphosphate
• Adenosine Triphosphatases
• Pyrophosphatases
• Apyrase

Topics

• Adenosine Triphosphatases (genetics)
• Adenosine Triphosphate (metabolism)
• Animals
• Apyrase (genetics)
• Homocysteine (pharmacology)
• Macrophages, Peritoneal (drug effects, metabolism)
• Male
• Mice
• Mice, Mutant Strains
• Pyrophosphatases (genetics)
• RNA, Messenger (metabolism)
• Receptors, Purinergic P1 (genetics)
• Receptors, Purinergic P2 (genetics)