ABSTRACT
Title
Monoamine oxidase activity over activation and oxidative stress in human failing heart from ischemic diseases
Authors
M.E. Manni1, C. Nediani2, G. d’Amati3, C. Giordano3, E. Bigagli1, E. Cerbai1 and L. Raimondi1
1Dept. of Pharmacology, University of Florence, Italy;
2Dept of Biochemical Science, University of Florence, Italy;
3Dept. of Radiology, Oncology and Pathology, University “La Sapienza” Rome, Italy.
1Dept. of Pharmacology, University of Florence, Italy;
2Dept of Biochemical Science, University of Florence, Italy;
3Dept. of Radiology, Oncology and Pathology, University “La Sapienza” Rome, Italy.
Abstract
Experimental evidence indicate that in myocardium, monoamine oxidase activity (MAO) may represent a source of ROS participating to ischemia-reperfusion injuries and a key event in the transition from cardiac hypertrophy towards failure.
We aimed to measure monoamine oxidases (MAO), catalase and aldehydedehydrogenase-2 (ALDH-2) activities, malonyldialdehyde (MDA) and carbonylated protein levels in the right (RV) and in the left ventricle (LF) from not failing (NF; n=4) and failing human hearts secondary to ischemic (IHD; n=7) and not ischemic (not-IHD; n=7) diseases.
MAO-A and B activity was assayed radiochemically using [14C]-serotonin and [14C]-benzylamine (100 µM, 1 µCi/ml) respectively. ALDH-2 and catalase activities, MDA and carbonylated proteins levels were measured spectrophotometrically.
MAO-B is the predominant isoform in both ventricles from NF hearts. In ventricles from IHD specimens, MAO A an B activity was found 5 and 6 times higher respectively than in NF ventricles and MAO B predominates over MAO A only in the LV. Instead, in not-IHD specimens, MAO activity was similar to that of NF with MAO B predominating over MAO A in both ventricles. In addition, MAO A activity was higher in the LV over the RV. Furthermore, oxidative stress markers, catalase and ALDH-2 activities increase in failing over NF ventricles with some differences. In fact, while MDA and ALDH-2 activity increased in both ventricles, carbonylated proteins levels increased only in the RV.
The main result of our work is that over activation of MAO, of enzyme scavenging MAO products of reactions and oxidative stress cluster in LV of failing hearts secondary to IHD. The clustering of these determinants may represent a typical feature of IHD participating to ROS-dependent reperfusion injuries up to failure.
We aimed to measure monoamine oxidases (MAO), catalase and aldehydedehydrogenase-2 (ALDH-2) activities, malonyldialdehyde (MDA) and carbonylated protein levels in the right (RV) and in the left ventricle (LF) from not failing (NF; n=4) and failing human hearts secondary to ischemic (IHD; n=7) and not ischemic (not-IHD; n=7) diseases.
MAO-A and B activity was assayed radiochemically using [14C]-serotonin and [14C]-benzylamine (100 µM, 1 µCi/ml) respectively. ALDH-2 and catalase activities, MDA and carbonylated proteins levels were measured spectrophotometrically.
MAO-B is the predominant isoform in both ventricles from NF hearts. In ventricles from IHD specimens, MAO A an B activity was found 5 and 6 times higher respectively than in NF ventricles and MAO B predominates over MAO A only in the LV. Instead, in not-IHD specimens, MAO activity was similar to that of NF with MAO B predominating over MAO A in both ventricles. In addition, MAO A activity was higher in the LV over the RV. Furthermore, oxidative stress markers, catalase and ALDH-2 activities increase in failing over NF ventricles with some differences. In fact, while MDA and ALDH-2 activity increased in both ventricles, carbonylated proteins levels increased only in the RV.
The main result of our work is that over activation of MAO, of enzyme scavenging MAO products of reactions and oxidative stress cluster in LV of failing hearts secondary to IHD. The clustering of these determinants may represent a typical feature of IHD participating to ROS-dependent reperfusion injuries up to failure.