Authors: Jinapath Lohakul, Saowanee Jeayeng, Anyamanee Chaiprasongsuk, Roberta Torregrossa, Mark Wood, Malinee Saelim, Weerawon Thangboonjit, Matthew Whiteman, Uraiwan
Summary: Aims: Oxidative stress and mitochondrial dysfunction play a role in the process of skin photoaging via activation of matrix metalloproteases (MMPs) and the subsequent degradation of collagen. The activation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor controlling antioxidant and cytoprotective defense systems, might offer a pharmacological approach to prevent skin photoaging. We therefore investigated might offer a pharmacological approach to prevent skin photoaging. We therefore investigated protective effect of the novel mitochondria-targeted hydrogen sulfide (H2S) delivery molecules AP39 and AP123, and non-targeted control molecules on UVA-induced photoaging in normal human dermal fibroblasts (NDHFs) in vitro and the skin of BALB/c mice in vivo.
Results: In NDHFs AP39 and AP123 (50-200 nM) but not non-targeted controls suppressed UVA (8 J/cm2)-mediated cytotoxicity and induction of MMP-1 activity, preserved cellular bioenergetics and increased the expression of collagen and nuclear levels of Nrf2. In in vivo experiments, topical application of AP39 or AP123 (0.3-1 µM/cm2; but not non-targeted control molecules) to mouse skin prior to UVA (60 J/cm2) irradiation prevented skin thickening, MMP induction, collagen loss oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased Nrf2-dependent signaling as well as increased manganese superoxide dismutase (MnSOD) levels and levels of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α).
Innovation and Conclusion: Targeting H2S delivery to mitochondria may represent a novel approach for the prevention and treatment of skin photoaging, as well as being useful tools for determining the role of mitochondrial H2S in skin disorders and aging.
Source: Antioxidants & Redox Signaling, 2021