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Monoamine oxidase activity promotes oxidative stress and cell death in cardiomyocytes exposed to high glucose
Author(s) -
Kaludercic Nina,
De Mario Agnese,
Paolocci Nazareno,
Di Lisa Fabio
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb367
Subject(s) - oxidative stress , pargyline , monoamine oxidase , reactive oxygen species , propidium iodide , programmed cell death , nadph oxidase , chemistry , mitochondrial respiratory chain , mitochondrion , respiratory chain , diabetic cardiomyopathy , apoptosis , mitochondrial ros , medicine , endocrinology , cardiomyopathy , biochemistry , biology , enzyme , heart failure
Mitochondrial respiratory chain and NADPH oxidase are described as major sources of reactive oxygen species (ROS) in diabetic cardiomyopathy. Oddly, the role of monoamine oxidase (MAO) has been overlooked so far. These mitochondrial flavoenzymes are responsible for oxidative stress and cell death in failing and ischemic/reperfused hearts. Here we assessed whether MAO contribute to high glucose (HG) induced cell damage. Neonatal rat cardiomyocytes were cultured in high glucose (HG, 30 mM) for 24 or 48 hours in the absence or presence of MAO inhibitor pargyline and compared to those cultured in normal (NG, 5 mM) or high mannitol (HM, 30mM) containing media. Mitochondrial ROS production, detected by Mitotracker Red, was significantly increased in HG myocytes (+40%, p<0.001) as compared to other cells. Pargyline completely prevented this increase. Apoptosis and necrosis, assessed by bisbenzimide and propidium iodide staining respectively, were 1.8 and 2‐fold higher in HG (p<0.05). MAO inhibition significantly reduced cell death both after 24 and 48 hours of culture in HG. In conclusion, here we demonstrate that MAO play a major role in the oxidative stress and cell death in cardiomyocytes exposed to HG. MAO may amplify the effects of existing ROS triggers or HG may directly enhance MAO activity. Both phenomena are likely to be relevant for the onset and progression of diabetic cardiomyopathy.