Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage

International Journal of Molecular Sciences

Alessia Leone¹  Michele Longo¹  Claudia Miele¹  Cecilia Nigro¹  Paola Mirra¹  Pietro Formisano¹  Gregory Alexander Raciti¹  Francesco Beguinot¹ 

[1]Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Council of Research, 80131 Naples, Italy

关键词: methylglyoxal;    glyoxalase;    vascular function;    insulin-resistance;   

DOI  :  10.3390/ijms18010188

来源: DOAJ

【 摘 要 】

The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs. MGO and its advanced glycated end products (AGEs) are associated with age-related diseases including diabetes, vascular dysfunction and neurodegeneration. Endothelial dysfunction is the first step in the initiation, progression and clinical outcome of vascular complications, such as retinopathy, nephropathy, impaired wound healing and macroangiopathy. Because of these considerations, studies have been centered on understanding the molecular basis of endothelial dysfunction in diabetes, unveiling a central role of MGO-Glo1 imbalance in the onset of vascular complications. This review focuses on the current understanding of MGO accumulation and Glo1 activity in diabetes, and their contribution on the impairment of endothelial function leading to diabetes-associated vascular damage.

【 授权许可】

Unknown