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Publication : Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes.

First Author  Baek JY Year  2017
Journal  J Invest Dermatol Volume  137
Issue  6 Pages  1333-1342
PubMed ID  28202400 Mgi Jnum  J:243315
Mgi Id  MGI:5908084 Doi  10.1016/j.jid.2017.01.027
Citation  Baek JY, et al. (2017) Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes. J Invest Dermatol 137(6):1333-1342
abstractText  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 H2O2 levels were differentiated from other types of ROS using mitochondria-specific fluorescent H2O2 indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient (PrxIII-/-) mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial H2O2 compared 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 H2O2 is 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.
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