title: Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes.
abstract: UVB light induces generation of reactive oxygen species, ultimately leading to skin cell damage. Mitochondria are a major source of reactive oxygen species in UVB-irradiated skin cells, with increased levels of mitochondrial reactive oxygen species having been implicated in keratinocyte apoptosis. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-removing enzyme in the mitochondria of most cell types. Here, the protective role of PrxIII against UVB-induced apoptosis of epidermal keratinocytes was investigated. Mitochondrial H2O2levels were differentiated from other types of ROS using mitochondria-specific fluorescent H2O2indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient (PrxIII-/-) mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial H2O2compared with PrxIII-expressing controls. Keratinocytes lacking PrxIII were subsequently sensitized to apoptosis through mitochondrial membrane potential loss, cardiolipin oxidation, cytochrome c release, and caspase activation. Increased UVB-induced epidermal tissue damage in PrxIII-/-mice was attributable to increased caspase-dependent keratinocyte apoptosis. Our findings show that mitochondrial H2O2is a key mediator in UVB-induced apoptosis of keratinocytes and that PrxIII plays a critical role in protecting epidermal keratinocytes against UVB-induced apoptosis through eliminating mitochondrial H2O2. These findings support the concept that reinforcing mitochondrial PrxIII defenses may help prevent UVB-induced skin damage such as inflammation, sunburn, and photoaging.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Baek
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Park
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Su Bin
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Sin Ri
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea; College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea; College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Lim
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea; College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea. Electronic address: changts@ewha.ac.kr.
authors.forename: Tong-Shin
authors.initials: TS
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000528:radiation effects*; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D051379:Mice; D061105:Peroxiredoxin III / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D061105:Peroxiredoxin III