Novel Antioxidant Tripeptide “ACQ” Can Prevent UV-Induced Cell Death and Preserve the Number of Epidermal Stem Cells

Abstract

We found that tripeptide “ACQ: alanine-cysteine-glutamine” has significant DPPH scavenging activity compared to that of glutathione. Antioxidant effects of ACQ were tested in in vitro and in vivo models. When treated with H2O2, mock treated fibroblasts and keratinocytes showed strong staining by H2DCFA. But, ACQ showed good protective effects against hydrogen peroxide treatment. When mice were fed for 2 or 4 weeks, similar protective effects were observed. In the control group, epidermis was severely damaged by UV irradiation and apoptotic keratinocytes were observed. There were also numerous TUNEL positive cells. But in the ACQ group, epidermis became thicker and there was no sign of severe damage. Interestingly, the number of p63 cells was also higher in ACQ fed mice. To confirm the stem cell rescuing effects of ACQ, three-dimensional skin samples were constructed. Results showed that ACQ increased the expression of integrin α6 and the number of p63 positive cells. These findings showed that ACQ has good antioxidant activity and may increase stem cell activities by the regulation of integrin α6.

Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging

“…Choi et al suggested that redox status is essential for stemness in skin equivalents and demonstrated that vitamin C, plant extracts ( G. lucidum and R. sachalinensis ), and a novel tripeptide “ACQ: alanine-cysteine-glutamine” having high antioxidant activities promoted stemness and the proliferative capacity of epidermal basal cells by improving microenvironment through regulation of integrins, the main receptors for ECM [ 167 , 168 ]. In addition to various antioxidant compounds reported as having beneficial effects on stemness of the skin, the use of adult stem cells and their niches to contribute to regeneration and repair of damaged tissues has been proposed as a promising strategy in cell-based therapy in tissue injury.…”

Antioxidants as an Epidermal Stem Cell Activator

“…Furthermore, activation of integrin β1 is involved in the inhibition of differentiation signals via extracellular signal-regulated kinases (ERK) signaling pathway [ 26 ]. These findings suggest integrins are important in regulating stem cell physiology and determining the fate of epidermal stem cells in skin [ 11 ].…”

“…Since skin constitutes the outer surface of human body that is constantly exposed to environmental stimuli, the epidermal stem cells are regulated by not only the interaction with intrinsic transcriptional regulations but also extrinsic environmental signals [ 11 ]. These extrinsic factors could affect stem cell microenvironment, altering the fate of epidermal stem cells [ 28 ].…”

“…In an effort to find a novel short bioactive antioxidant peptide that allows transcutaneous delivery, we screened peptide library that contains cysteine. We found a novel tripeptide alanine-cysteine-glutamine (ACQ) that has more significant antioxidant property compared with that of glutathione [ 11 ]. ACQ protected fibroblasts and keratinocytes from the hydrogen peroxide-induced oxidative stress.…”

“…Our team has studied the effect of antioxidants on the interfollicular epidermal stem cells [ 7 , 8 , 9 , 10 , 11 , 12 ]. Well-known antioxidants such as ascorbic acid, resveratrol and copper-GHK, as well as plant extracts that have been used for anti-fatigue or anti-stress treatment in traditional medicines have been evaluated for their role to activate the proliferative potential of epidermal stem cells.…”