Serotonin-mediated protein carbonylation in the right heart.
Pulmonary hypertension is a devastating disease, which leads to right heart failure. Serotonin (5-HT) plays important roles in the pathogenesis of pulmonary hypertension and pulmonary vascular remodeling. The role of 5-HT in right heart failure, however, is unknown. Since oxidative stress may mediate heart failure, the present study examined the effects of 5-HT on protein oxidation in the adult rat right heart ventricle. Treatment of perfused isolated hearts with 5-HT resulted in the promotion of protein carbonylation, specifically in the right ventricle, but not in the left. While no differences between right and left ventricular antioxidant enzymes and 5-HT receptors/transporter were detected, monoamine oxidase A (MAO-A) expression and activity were found to be lower in the right ventricle compared to the left. These results indicate that differences in neither the reactive oxygen species (ROS) scavenging ability, 5-HT membrane signaling capacity, nor MAO-dependent production of hydrogen peroxide are responsible for varied 5-HT-mediated protein carbonylation in right and left ventricles. Rather, lower MAO-A in the right heart might preserve cytosolic 5-HT which triggers other mechanisms for ROS production. Consistently, inhibition of MAO-A resulted in the promotion of protein carbonylation. We propose that low MAO-A, thus reduced degradation of 5-HT, increases the intracellular 5-HT activity in the right ventricle, leading to the promotion of protein carbonylation.
Liu
Lingling
L
Department of Pharmacology, Georgetown University Medical Center, NW403 Medical-Dental Building, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Marcocci
Lucia
L
Wong
Chi Ming
CM
Park
Ah-Mee
AM
Suzuki
Yuichiro J
YJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000502:physiology*
D000975:Antioxidants; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin