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Int J Mol Sci. 2017 Jan 18;18(1). pii: E188. doi: 10.3390/ijms18010188.

Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage.

Nigro C1,2, Leone A3,4, Raciti GA5,6, Longo M7,8, Mirra P9,10, Formisano P11,12, Beguinot F13,14, Miele C15,16.

Author information

1
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. cecilia.nigro@alice.it.
2
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. cecilia.nigro@alice.it.
3
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. aleleone86@libero.it.
4
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. aleleone86@libero.it.
5
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. gregoryraciti@gmail.com.
6
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. gregoryraciti@gmail.com.
7
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. mi_longo@libero.it.
8
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. mi_longo@libero.it.
9
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. paolamirra.lib@libero.it.
10
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. paolamirra.lib@libero.it.
11
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. fpietro@unina.it.
12
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. fpietro@unina.it.
13
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. beguino@unina.it.
14
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. beguino@unina.it.
15
Research Unit (URT) of the Institute of Experimental Endocrinology and Oncology "G. Salvatore", National Council of Research, 80131 Naples, Italy. c.miele@ieos.cnr.it.
16
Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy. c.miele@ieos.cnr.it.

Abstract

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.

KEYWORDS:

glyoxalase; insulin-resistance; methylglyoxal; vascular function

PMID:
28106778
PMCID:
PMC5297820
DOI:
10.3390/ijms18010188
[Indexed for MEDLINE]
Free PMC Article

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