Enzymatic Deglycation of Damaged Skin by Means of Combined Treatment of Fructosamine-3-Kinase and Fructosyl-Amino Acid Oxidase

Abstract

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment.

Fructosyl Amino Oxidase as a Therapeutic Enzyme in Age-Related Macular Degeneration

“…In agreement with earlier observations on FN3K, our observations strengthen our hypothesis that the process of non-enzymatic glycation of long-lived proteins can be reversed [15,[20][21][22]. The absence of any chemical effect following administration of the inactive mutant FAOD enzyme proves that the observed changes following FAOD treatment are due to the catalytic activity of the FAOD, per se.…”

“…However, intact hemoglobin A1c is unable to react with FAOD and, thus, specimens require a preparative proteolytic digestion step to liberate glycated amino acids or glycated dipeptides [19]. As a result, the therapeutic use of FAOD in AGEs-induced conditions in animals or humans has only recently been considered in the treatment of glycation-associated disorders such as presbyopia and hypertrophic scars [20,21].…”