β-N-Methylamino-L-Alanine (BMAA) Modulates the Sympathetic Regulation and Homeostasis of Polyamines

Abstract

The neurotoxin β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim of this research is to study the toxicity of BMAA (0.1–1 mM) on mitochondria and submitochondrial particles with ATPase activity, on the semicarbazide-sensitive amino oxidases (SSAOs) activity of rat liver, and on an in vitro model containing functionally active excitable tissues—regularly contracting heart muscle preparation with a preserved autonomic innervation. For the first time the BMAA-dependent inhibition of SSAO activity, the elimination of the positive inotropic effect of adrenergic innervation, and the direct and reversible inhibition of adrenaline signaling in ventricular myocytes with 1 mM BMAA were observed. Additionally, it is confirmed that 1 mM BMAA can activate mitochondrial ATPase indirectly. It is concluded that a higher dose of BMAA may influence multiple physiological and pathological processes as it slows down the degradation of biogenic amines, downregulates the sympathetic neuromediation, and embarrasses the cell signaling of adrenergic receptors.

Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging

“…Part of their toxicity depends on increased ROS production and decreased cellular antioxidant capacity [238], and the references therein. The cyanotoxins cylindrospermopsin (CYN), β-N-methylamino-L-alanine (BMAA), microcystins and nodularins decrease cell redox potential and attenuate mitochondrial function, the main ROS producer, leading to decreased cell viability with intensive metabolism in the first line, the neurons [239][240][241][242]. CYN leads to oxidative stress, either directly or indirectly by reducing GSH formation [240].…”