Methionine and methionine sulfoxide induces neurochemical and morphological changes in cultured astrocytes: Involvement of Na+, K+-ATPase activity, oxidative status, and cholinergic and purinergic signaling.

Abstract

Hypermethioninemia is an inherited metabolic disorder characterized by high concentration of methionine (Met) and its metabolites such as methionine sulfoxide (Met-SO), which may lead to development of neurological alterations. The aim of this study was to investigate the in vitro effects of Met or Met-SO on viability, proliferation, morphology, and neurochemical parameters in primary culture of cortical astrocytes, after treatment with 1 or 2 mM Met or 0.5 mM Met-SO, for 24, 48, and 72 h. Met or Met-SO did not affect cell viability and proliferation but induced astrocyte hypertrophy. Acetylcholinesterase activity was increased, while Na+, K+-ATPase activity was decreased by 2 mM Met, Met-SO, or Met (1 and 2 mM) + Met-SO (P < 0.05). ATP and AMP hydrolysis was decreased by Met (1 and 2 mM), Met-SO and Met (1 and 2 mM) + Met-SO treatment, while ADP hydrolysis was enhanced by Met-SO and Met (1 and 2 mM) + Met-SO (P < 0.05). Superoxide dismutase activity was increased by Met-SO and Met (1 and 2 mM) + Met-SO (P < 0.05). Catalase and glutathione S-transferase activities were reduced by Met or Met-SO treatment for 48 and 72 h (P < 0.05). Reactive oxygen species and total thiol content was reduced by Met or Met-SO treatment for 24, 48, and 72 h while nitrite and thiobarbituric acid reactive substance levels were increased under the same experimental conditions (P < 0.05). High concentrations of Met and Met-SO do not cause cell death but induced changes in astrocyte function. These alterations in astrocytic homeostasis may be associated with neurological symptoms found in hypermethioninemia.

• Authors: Mayara Sandrielly Pereira Soares, Nathalia Stark Pedra, Natália Pontes Bona, Anita Ávila de Souza, Fernanda Cardoso Teixeira, Juliana Hofstatter Azambuja, Angela Ts Wyse, Elizandra Braganhol, Francieli Moro Stefanello, Roselia Maria Spanevello
• Journal: Neurotoxicology (Neurotoxicology) Vol. 77 Pg. 60-70 (03 2020) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 31883448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Adenosine Triphosphate
• Methionine
• Acetylcholinesterase
• Sodium-Potassium-Exchanging ATPase
• methionine sulfoxide

Topics

• Acetylcholinesterase (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Astrocytes (drug effects, metabolism, pathology)
• Cells, Cultured
• Methionine (analogs & derivatives, toxicity)
• Oxidative Stress (drug effects)
• Rats, Wistar
• Signal Transduction (drug effects)
• Sodium-Potassium-Exchanging ATPase (metabolism)