The Protein Deacetylase SIRT3 Prevents Oxidative Stress-induced Keratinocyte Differentiation

Bause, Alexandra S.; Matsui, Mary S.; Haigis, Marcia C.

doi:10.1074/jbc.m113.472324

Cited by 26 publications

(19 citation statements)

References 25 publications

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“…The CYGB gene is an interesting example of a gene that is functionally transcriptional activated by p63 during the regulation of cellular ROS via a pathway linked to both stress responses and ROS homeostasis during cell proliferation/differentiation. [26][27][28][29][30] Both normal keratinocytes in vitro and keratinocytes in the basal layer of the epidermis express Cygb and have a reduced sensitivity to oxidative stress. Indeed, treating keratinocytes with H 2 O 2 for 18 h increases CYGB expression (at both the mRNA and protein levels) (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

“…ROS formation is modulated during oxidative metabolism, oxidative stress, apoptosis, ageing and cancer; however, increasing evidence demonstrates that ROS are useful signalling molecules that modulate growth and differentiation when expressed at physiological concentrations. [26][27][28][29][30] Here we report that the cytoglobin (CYGB) gene encoding the cytoglobin protein, Cygb, which is expressed in several cell types, is transcriptionally regulated by ΔNp63. Furthermore, this regulation has important roles in maintaining physiological ROS levels in proliferating keratinocytes and in protecting these cells from oxidative stress and stress-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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ΔNp63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer

et al. 2015

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During physiological aerobic metabolism, the epidermis undergoes significant oxidative stress as a result of the production of reactive oxygen species (ROS). To maintain a balanced oxidative state, cells have developed protective antioxidant systems, and preliminary studies suggest that the transcriptional factor p63 is involved in cellular oxidative defence. Supporting this hypothesis, the ΔNp63α isoform of p63 is expressed at high levels in the proliferative basal layer of the epidermis. Here we identify the CYGB gene as a novel transcriptional target of ΔNp63 that is involved in maintaining epidermal oxidative defence. The CYGB gene encodes cytoglobin, a member of the globin protein family, which facilitates the diffusion of oxygen through tissues and acts as a scavenger for nitric oxide or other ROS. By performing promoter activity assays and chromatin immunoprecipitation, reverse transcriptase quantitative PCR and western blotting analyses, we confirm the direct regulation of CYGB by ΔNp63α. We also demonstrate that CYGB has a protective role in proliferating keratinocytes grown under normal conditions, as well as in cells treated with exogenous hydrogen peroxide. These results indicate that ΔNp63, through its target CYGB has an important role in the cellular antioxidant system and protects keratinocytes from oxidative stress-induced apoptosis. The ΔNp63-CYGB axis is also present in lung and breast cancer cell lines, indicating that CYGB-mediated ROS-scavenging activity may also have a role in epithelial tumours. In human lung cancer data sets, the p63-CYGB interaction significantly predicts reduction of patient survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ΔNp63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer

et al. 2015

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“…20 The mean fluorescence intensity of cells detected at 488 nm excitation and 585 nm emission was determined. 20 The mean fluorescence intensity of cells detected at 488 nm excitation and 585 nm emission was determined.…”

Section: Reactive Oxygen Species Productionmentioning

confidence: 99%

Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS‐sirt1‐NF‐κB signaling

Wang

Zhang

et al. 2018

J of Cellular Biochemistry

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Psoriasis is a chronic disease which carries the emotional and social burden, promotes joint disability and raises comorbidity possibility in patients. Obesity is closely correlated with the occurrence of psoriasis and adipokines produced by adipose tissues were found to be critical culprits. Chemerin is one of them and its expression was increased in patients with psoriatic arthritis. In our hypothesis, chemerin might act on keratinocytes and promote an inflammatory response, which plays an essential role in psoriatic epidermis. To validate our hypothesis, HaCaT cells and primary human keratinocytes were treated with chemerin (5, 10, and 20 ng/mL for 24 hours). Enzyme‐linked immunosorbent assay (ELISA) was used to determine the secretion of inflammatory factors. Nuclear factor‐κB (NF‐κB) activation and p65 acetylation were evaluated by Western blot analysis. The expression and activity of sirtuin 1 (sirt1), a deacetylase act on p65, were also analyzed. The results showed that chemerin prompted inflammatory factors secretion, NF‐κB activation and p65 acetylation through chemerin receptor 23 receptor. Chemerin constrained the expression and deacetylase activity of sirt1 through augment of reactive oxygen species (ROS) production. Additionally, chemerin exacerbated psoriasiform dermatitis in imiquimod‐treated mice model. In conclusion, chemerin can seduce inflammatory response and promote NF‐κB activation through inhibition of sirt1 activity by ROS production.

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“…One intriguing problem is that the acetylation sites identified in SOD2 in humans are different from those in mice; for instance, K122 is the acetylation site in mice, whereas K68 is the acetylation site in humans [30]. The deacetylation of these lysine residues in SOD2 is catalyzed by SIRT3 [30], a mitochondrial deacetylase [32] of the sirtuin family that functions in the regulation of antioxidative responses [33][34][35]. Although the deacetylation-mediated SOD2 activation seems to be clearly illustrated in the aforementioned studies, the mechanism underlying this activation by which the acetylation site exactly determines the SOD2 activity in humans and whether there may exist any unknown sites that are also involved in SIRT3-mediated deacetylation of SOD2 remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Novel mechanisms for superoxide-scavenging activity of human manganese superoxide dismutase determined by the K68 key acetylation site

Lü

Cheng

Zhang

et al. 2015

Free Radical Biology and Medicine

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The Protein Deacetylase SIRT3 Prevents Oxidative Stress-induced Keratinocyte Differentiation

Cited by 26 publications

References 25 publications

ΔNp63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer

ΔNp63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer

Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS‐sirt1‐NF‐κB signaling

Novel mechanisms for superoxide-scavenging activity of human manganese superoxide dismutase determined by the K68 key acetylation site

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