Monoamine oxidases as sources of oxidants in the heart

Abstract

Oxidative stress can be generated at several sites within the mitochondria. Among these, monoamine oxidases (MAO) have been described as a prominent source. MAO are mitochondrial flavoenzymes responsible for the oxidative deamination of catecholamines, serotonin and biogenic amines, and during this process they generate H2O2 and aldehyde intermediates. The role of MAO in cardiovascular pathophysiology has only recently gathered some attention since it has been demonstrated that both H2O2 and aldehydes may target mitochondrial function and consequently affect function and viability of the myocardium. In the present review, we will discuss the role of MAO in catecholamine and serotonin clearance and cycling in relation to cardiac structure and function. The relevant contribution of each MAO isoform (MAO-A or -B) will be discussed in relation to mitochondrial dysfunction and myocardial injury. Finally, we will examine both beneficial effects of their pharmacological or genetic inhibition along with potential adverse effects observed at baseline in MAO knockout mice, as well as the deleterious effects following their over-expression specifically at cardiomyocyte level.

Monoamine oxidase‐A is a novel driver of stress‐induced premature senescence through inhibition of parkin‐mediated mitophagy

“…MAO‐A‐driven H 2 O 2 production has been previously assigned to different types of cellular responses, such as hypertrophy and death (Kaludercic et al, 2014). In addition, elevated MAO‐A expression in prostate cancer cells was recently shown to promote metastasis by two distinct mechanisms—epithelial‐to‐mesenchymal transition and paracrine Shh signalling (Wu et al, 2014, 2017 ).…”

“…In the heart, MAO‐A has been demonstrated to be an important source of oxidative stress in acute and chronic pathological conditions (Bianchi et al, 2005; Kaludercic et al, 2010). In particular, cardiac overexpression of MAO‐A drives oxidative stress and mitochondrial damage, leading to cell death and heart failure (Kaludercic, Mialet‐Perez, Paolocci, Parini, & Di Lisa, 2014; Villeneuve et al, 2013). Notably, all these effects are observed with high levels of MAO‐A activation, and it is well‐established that depending on its concentration, H 2 O 2 can have multiple dose‐dependent cellular responses, ranging from proliferation to necrosis (Giorgio, Trinei, Migliaccio, & Pelicci, 2007).…”

Molecular aspects of monoamine oxidase B

“…Studies in this area since 2002 when the importance of amine plus MAO-generated oxidative stress became apparent, and some insights into the mechanisms involved are reviewed in (Kaludercic et al, 2014). More recently, MAO has been noted as a source of oxidative stress in diabetes (Sturza et al, 2015).…”

“…A further benefit of inhibiting MAO is the decreased production of ammonia and hydrogen peroxide that accompany amine oxidation, thus reducing oxidative stress (Kaludercic et al, 2014, Ooi et al, 2015.…”

Monoamine oxidase inhibitory activities of heterocyclic chalcones

“…12 The by-products of MAO-catalysis may target mitochondrial function and in this way affect the function and viability of the myocardium. 13 Based on these considerations, MAO inhibitors are of importance in medicine and numerous research groups are involved in the discovery of novel MAO inhibitors of both natural and synthetic origin. Chalcones (1,3-diphenyl-2-propen-1-ones) ( a class of compounds that have been shown to inhibit the MAOs (Fig.…”