A Powerful Mitochondria-Targeted Iron Chelator Affords High Photoprotection against Solar Ultraviolet A Radiation.
Mitochondria are the principal destination for labile iron, making these organelles particularly susceptible to oxidative damage on exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The labile iron-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via adenosine triphosphate depletion. Therefore, targeted removal of mitochondrial labile iron via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria-homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, adenosine triphosphate depletion, and the ensuing necrotic cell death in skin fibroblasts, and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of the UVA component of sunlight.
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, UK.
Olivier
O
Reelfs
Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, London, UK.
Vincenzo
V
Abbate
Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, London, UK.
Robert C
RC
Hider
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, UK. Electronic address: prscap@bath.ac.uk.
Charareh
C
Pourzand
D000255:Adenosine Triphosphate / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000737:chemistry*; D008027:Light; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010777:Photochemistry; D012867:Skin / Q000378:metabolism; D013472:Sunlight; D014466:Ultraviolet Rays
D000975:Antioxidants; D007502:Iron Chelating Agents; D010455:Peptides; D000255:Adenosine Triphosphate; D007501:Iron; D010100:Oxygen