Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats

Abstract

Oxidative stress is one of the factors involved in age-related impairment of cardiac function. In the present study, we investigated the role of the catecholamine-degrading enzyme monoamine oxidase (MAO) in H(2)O(2) production in the hearts of young, adult, and old rats. MAO-dependent H(2)O(2) production, measured by a chemiluminescence-based assay, increased with age, reaching the maximum in 24-mo-old rats (7.5-fold increase vs. 1-mo-old rats). The following observations indicate that the age-dependent increase in H(2)O(2) generation was fully related to the MAO-A isoform: 1) at all the ages tested, chemiluminescence production was inhibited by the MAO-A inhibitor clorgyline but not by the MAO-B inhibitor RO-19 6327; 2) enzyme assay, Western blot, and semiquantitative RT-PCR analysis showed an age-dependent increase in cardiac MAO-A activity, immunodetection, and mRNA expression, respectively; and 3) the MAO-B isoform was undetectable by enzyme assay and Western blot analysis. These results suggest that MAO-A could be a major source of H(2)O(2) in the aging heart.

Oxidized CaMKII causes cardiac sinus node dysfunction in mice

“…Age-related SND is well recognized (8), but the basis for progressive, age-related reductions in maximal fight-or-flight HR responses to exercise in healthy persons and animals is not well understood. Old rats have increased myocardial oxidation (49) and reduced HR compared with younger animals, and old rats were recently reported to have a reduced SAN cell mass compared with young rats (17), suggesting the hypothesis that SND due to normal aging could also be due to increased oxCaMKII and SAN cell loss. Our computational model suggests that a critical mass of SAN cells is necessary to maintain a physiological diastolic depolarization rate, impulse formation, and conduction velocity.…”

Mitochondria and aging: A role for the mitochondrial transition pore?

“…Evidence also suggests that aging involves a change in ROS regulatory processes encompassing a decline in mitochondrial function and an increase in ROS generation (Brand, 2014; Bratic & Larsson, 2013; Skulachev & Skulachev, 2014). For instance, monoamine oxidase activity in 24‐month‐old rat cardiac mitochondria was much stronger than that in 1‐month‐old rats, showing that monoamine oxidase may be an important source of ROS in the aging heart (Di Lisa, Kaludercic, Carpi, Menabo, & Giorgio, 2009; Maurel et al., 2003). In this context, an interesting relationship was found between the rate of ROS production during mitochondrial reverse electron transport in vitro and lifespan in vertebrate homeotherms (Lambert et al., 2007).…”

Is defective electron transport at the hub of aging?

“…The outer membrane of skeletal muscle mitochondria was already known to contain two enzymes oxidizing tyramine, MAOA and MAOB (Kalaria & Haric, 1987), each one potentially able to compensate for any decline of activity by the other. The activity of each form is known to increase many-fold with age in other tissues (Saura et al ., 1997;Maurel et al ., 2003) and lower MAOB activity in platelets is associated with smoking, gender and life-long alcohol consumption (Snell et al ., 2002). That complexes I and IV seemed to undergo disproportionate losses of activity with age was later corroborated with matrix citrate synthase activity as reference (Cooper et al ., 1992).…”