Methyl glyoxal is a reactive dicarbonyl precursor of advanced glycation end products (AGEs). AGEs play an important role in the development and progression of cardiovascular diseases in diabetes. Serum levels of AGEs in patients with type 2 diabetes with coronary heart disease 8CHD) are increased compared to patients without CHD, and correlate with CHD severity. Methylglyoxal is effectively detoxifies by the glyoxalase system, that comprises glyoxalase 1 and 2. overexpression of glyoxalase 1 prevents the accumulation of intracellular methylglyoxal and AGEs in endothelial cells exposed to high glucose concentration. Recently it has been demonstrated that glyoxalase 1 expression is regulated by the nuclear factor E2-related factor 2 (Nrf2). Sulforaphane is an isothacianate formed form glucoraphanin present in Cruciferous vegetables. As SF is a potent inducer of Nrf2-modulated phase II enzymes, we investigated its protective effect against methylglyoxal-induced damage in primary cultures of rat cardiomyocytes. Cell viability was evaluated by MTT assay, caspase 3 activity by a fluorimetric method, caspase 3 and glyoxalase 1 expression by immunoblotting, glyoxalase 1 activity spectrophotometrically and ROS production by the 2’,7’ dichlorofluorescein-diacetate assay. We observed that methylglyoxal reduced cardiomyocyte viability, induced apoptotic cell death and increased ROS production. Sulforaphane treatment significantly increased cell viability, and reduced apoptotic cell death and ROS production of methylglyoxal-damaged cardiomyocytes. Moreover, for the first time, we demonstrated the sulforaphane is able to significantly increase glyoxalase1 protein expression and activity. These findings suggest that targeting glyoxalase system might be a promising therapeutic strategy to counteract cardiovascular diseases of diabetic patients.

Sulforaphane counteracts glycative stress in cardiomyocytes through glyoxalase 1 induction

ANGELONI, CRISTINA;FABBRI, DANIELE;HRELIA, SILVANA
2012

Abstract

Methyl glyoxal is a reactive dicarbonyl precursor of advanced glycation end products (AGEs). AGEs play an important role in the development and progression of cardiovascular diseases in diabetes. Serum levels of AGEs in patients with type 2 diabetes with coronary heart disease 8CHD) are increased compared to patients without CHD, and correlate with CHD severity. Methylglyoxal is effectively detoxifies by the glyoxalase system, that comprises glyoxalase 1 and 2. overexpression of glyoxalase 1 prevents the accumulation of intracellular methylglyoxal and AGEs in endothelial cells exposed to high glucose concentration. Recently it has been demonstrated that glyoxalase 1 expression is regulated by the nuclear factor E2-related factor 2 (Nrf2). Sulforaphane is an isothacianate formed form glucoraphanin present in Cruciferous vegetables. As SF is a potent inducer of Nrf2-modulated phase II enzymes, we investigated its protective effect against methylglyoxal-induced damage in primary cultures of rat cardiomyocytes. Cell viability was evaluated by MTT assay, caspase 3 activity by a fluorimetric method, caspase 3 and glyoxalase 1 expression by immunoblotting, glyoxalase 1 activity spectrophotometrically and ROS production by the 2’,7’ dichlorofluorescein-diacetate assay. We observed that methylglyoxal reduced cardiomyocyte viability, induced apoptotic cell death and increased ROS production. Sulforaphane treatment significantly increased cell viability, and reduced apoptotic cell death and ROS production of methylglyoxal-damaged cardiomyocytes. Moreover, for the first time, we demonstrated the sulforaphane is able to significantly increase glyoxalase1 protein expression and activity. These findings suggest that targeting glyoxalase system might be a promising therapeutic strategy to counteract cardiovascular diseases of diabetic patients.
Oxidants and Antioxidants in Biology- Cell Signaling and Nutrient-Gene Interactions
64
64
C. Angeloni; D. Fabbri; S. Hrelia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/124154
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