Abstract
Dicarbonyl compounds, including methylglyoxal (MGO) and glyoxal (GO), are mainly formed as byproducts of glucose metabolism. The main glyoxalase system consists of glyoxalase I and II (Glo1 and Glo2) and is the main enzyme involved in the detoxification of dicarbonyl stress, which occurs as an accumulation of MGO or GO due to decreased activity or expression of Glo1. Dicarbonyl stress is a major cause of cellular and tissue dysfunction that causes various health issues, including diabetes, aging, and cancer. The skin is the largest organ in the body. In this review, we discuss the role of the glyoxalase system in the progression of skin aging, and more importantly, skin malignancies. We also discuss the future prospects of the glyoxalase system in other skin abnormalities such as psoriasis and vitiligo, including hyperpigmentation. Finally, in the present review, we suggest the role of glyoxalase in the progression of skin aging and glyoxalase system as a potential target for anticancer drug development for skin cancer.
Highlights
Dicarbonyl stress is the abnormal accumulation of highly reactive α-oxoaldehydes, such as methylglyoxal (MGO), glyoxal (GO), 3-deoxyglucosone (3-DG), and other dicarbonyl metabolites, leading to cell and tissue dysfunctions causing various health issues, including diabetes, renal failure, aging, and cancer
As Glo1 is highly expressed in both melanoma and non-melanoma skin cancer, we proposed that Glo1 is a novel target in skin cancer and more extensive studies are necessary in future animal and clinical studies for future drug development against skin cancer
Extensive investigation is needed to study the role of glyoxalase enzymes in various skin abnormalities, including hyperpigmentation, psoriasis, vitiligo, and atopic dermatitis (AD)
Summary
Dicarbonyl stress is the abnormal accumulation of highly reactive α-oxoaldehydes, such as methylglyoxal (MGO), glyoxal (GO), 3-deoxyglucosone (3-DG), and other dicarbonyl metabolites, leading to cell and tissue dysfunctions causing various health issues, including diabetes, renal failure, aging, and cancer. This is mainly due to the imbalance in the formation and metabolism of dicarbonyl metabolites via glucose metabolism. The glyoxalase system plays an important role in suppressing dicarbonyl stress and maintaining the dicarbonyl metabolites at low tolerable levels, preventing protein and cell dysfunction. Glyoxalase is present in epidermal keratinocytes and dermal fibroblasts, and plays a crucial role in skin homeostasis [1].
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