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 HO-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 HO levels were differentiated from other types of ROS using mitochondria-specific fluorescent HO indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient (PrxIII) mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial HO 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 HO 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 HO. These findings support the concept that reinforcing mitochondrial PrxIII defenses may help prevent UVB-induced skin damage such as inflammation, sunburn, and photoaging.

<p>Induction of Autophagy by Baicalin Through the AMPK-mTOR Pathway Protects Human Skin Fibroblasts from Ultraviolet B Radiation-Induced Apoptosis</p>

“…To investigate whether baicalin affects apoptosis induced by UVB in HSFs, Annexin V/PI staining and flow cytometry were applied. As Figure 2A and B shows, compared to the sham group, UVB irradiation (600 J/m 2 ) significantly induced apoptosis of HSFs (p < 0.05), which is in accordance with previous studies, 23,24 whilst baicalin treatment (25 ng/mL) inhibited apoptosis remarkably (p < 0.05). We further analyzed the possible pathway involved by exploring the expression of caspase 3, the key mediator in apoptosis, and PARP, the typical substrate for caspase 3.…”

Human Keratinocyte UVB-Protective Effects of a Low Molecular Weight Fucoidan from Sargassum horneri Purified by Step Gradient Ethanol Precipitation

“…The mitochondria-mediated apoptosis pathway is considered a major signaling route mediating apoptosis; the underlying mechanism can vary based on the type of cell, stimulus and other factors. Oxidative stress resulting from multiple factors, including the induction of UVB-radiation is reported to activate the mitochondria-mediated apoptosis pathway [18]. The pathway is initiated with the permeabilization of the mitochondrial outer membrane.…”

“…Cell death due to UVB-induced oxidative stress is reported to proceed via apoptosis [18]. Thus, we assessed apoptotic body formation and DNA damage.…”

Knockout Mouse Models for Peroxiredoxins

“…Increased oxidative stress in Prdx3 −/− shows placental defects, including focal necrosis and hyaline degeneration in trophoblast giant cells and vessel degeneration [83,84]. PRDX3 also has a protective role in UV-induced apoptosis of epidermal keratinocytes [85].…”