Nrf2 deficiency causes lipid oxidation, inflammation, and matrix-protease expression in DHA-supplemented and UVA-irradiated skin fibroblasts

Грубер, Флориан; Ornelas, Cayo Mecking; Karner, Susanne; Narzt, Marie-Sophie; Nagelreiter, Ionela-Mariana; Gschwandtner, Maria; Bochkov, Valery N.; Tschachler, Erwin

doi:10.1016/j.freeradbiomed.2015.05.006

Cited by 35 publications

(18 citation statements)

References 83 publications

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“…These results suggest that UV-A activates Nrf2 and its regulated antioxidant defense. This finding is supported by previous reports that UV-A irradiation with a fluence of 5 to 37.2 J/cm 2 leads to the induction of Nrf2-regulated antioxidant HO-1 in dermal fibroblasts 22 – 24 and keratinocytes, 25 , 38 retinal pigment epithelial cells 39 as well as mouse embryonic fibroblasts. 40 Studies on skin fibroblasts demonstrated that UV-A irradiation resulted in an increase in Nrf2 and its regulated gene HO-1at both the mRNA 22 and protein 24 level.…”

Section: Discussionsupporting

confidence: 90%

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UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells

Liu

Vojnovic

Kochevar

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeTo examine whether Nrf2-regulated antioxidant defense and p53 are activated in human corneal endothelial cells (CEnCs) by environmental levels of ultraviolet A (UV-A), a known stimulator of oxidative stress.MethodsImmortalized human CEnCs (HCEnCi) were exposed to UV-A fluences of 2.5, 5, 10, or 25 J/cm2, then allowed to recover for 3 to 24 hours. Control HCEnCi did not receive UV-A. Reactive oxygen species (ROS) were measured using H2DCFDA. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. Levels of Nrf2, HO-1, NQO-1, p53, and caspase3 were detected by immunnoblotting or real-time PCR. Activated caspase3 was measured by immunoblotting and a fluorescence assay.ResultsExposure of HCEnCi to 5, 10, and 25 J/cm2 UV-A increased ROS levels compared with controls. Nrf2, HO-1, and NQO-1 mRNA increased 1.7- to 3.2-fold at 3 and 6 hours after irradiation with 2.5 and 5 J/cm2 UV-A. At 6 hours post irradiation, UV-A (5 J/cm2) enhanced nuclear Nrf2 translocation. At 24 hours post treatment, UV-A (5, 10, and 25 J/cm2) produced a 1.8- to 2.8-fold increase in phospho-p53 and a 2.6- to 6.0-fold increase in activated caspase3 compared with controls, resulting in 20% to 42% cell death.ConclusionsLower fluences of UV-A induce Nrf2-regulated antioxidant defense and higher fluences activate p53 and caspase3, indicating that even near-environmental levels of UV-A may affect normal CEnCs. This data suggest that UV-A may especially damage cells deficient in antioxidant defense, and thus may be involved in the etiology of Fuchs' endothelial corneal dystrophy (FECD).

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Section: Discussionsupporting

confidence: 90%

“…20 , 21 At present, the interaction of Nrf2 and p53 under UV-A–induced oxidative damage remains unclear. 22 – 31 …”

mentioning

confidence: 99%

UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells

Liu

Vojnovic

Kochevar

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…These findings represent the first evidence of a direct interface between CFTR and Nrf2. Given the association of Nrf2 with the resolution of inflammation (11,12,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), our studies suggest that sufficient correction of CFTR function has the potential to modulate inflammatory signaling in CF.…”

Section: Introductionmentioning

confidence: 83%

Clinically approved CFTR modulators rescue Nrf2 dysfunction in cystic fibrosis airway epithelia

Borcherding¹,

Siefert²,

Lin³

et al. 2019

Journal of Clinical Investigation

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“…FOXO1 is a longevity transcription factor42 that promotes repair of DNA oxidative damage, together with the NF-E2 transcription factor43 whose motifs were presently identified in the promoters of the HMOX1, FTH1, and SQSTM1 genes. NRF2, whose motif was found in the SQSTM1 promoter region, is well known for its involvement in oxidative stress responses44 and photoaging resistance 45. EGR1 induces cell apoptosis upon UV irradiation stress,46 and its involvement presupposes an involvement of estrogen receptor (ESR1) in CSE-induced signaling, as shown in Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures

Yoshino

Polouliakh

Meguro

et al. 2016

CIA

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Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.

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Nrf2 deficiency causes lipid oxidation, inflammation, and matrix-protease expression in DHA-supplemented and UVA-irradiated skin fibroblasts

Cited by 35 publications

References 83 publications

UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells

UV-A Irradiation Activates Nrf2-Regulated Antioxidant Defense and Induces p53/Caspase3-Dependent Apoptosis in Corneal Endothelial Cells

Clinically approved CFTR modulators rescue Nrf2 dysfunction in cystic fibrosis airway epithelia

Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures

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