| RRC ID |
6055
|
| 著者 |
Gruber F, Mayer H, Lengauer B, Mlitz V, Sanders JM, Kadl A, Bilban M, de Martin R, Wagner O, Kensler TW, Yamamoto M, Leitinger N, Tschachler E.
|
| タイトル |
NF-E2-related factor 2 regulates the stress response to UVA-1-oxidized phospholipids in skin cells.
|
| ジャーナル |
FASEB J
|
| Abstract |
Long-wavelength ultraviolet (UVA-1) radiation causes oxidative stress that modifies cellular molecules. To defend themselves against noxious oxidation products, skin cells produce detoxifying enzymes and antioxidants. We have recently shown that UVA-1 oxidized the abundant membrane phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), which then induced the stress-response protein heme oxygenase 1 (HO-1) in dermal fibroblasts. Here we examined the effects of UVA-1- and UV-oxidized phospholipids on global gene expression in human dermal fibroblasts and keratinocytes. We identified a cluster of genes that were coinduced by UVA-1-oxidized PAPC and UVA-1 radiation. The cluster included HO-1, glutamate-cysteine ligase modifier subunit, aldo-keto reductases-1-C1 and -C2, and IL-8. These genes are members of the cellular stress response system termed "antioxidant response." Accordingly, the regulatory regions of all of these genes contain binding sites for NF-E2-related factor 2 (NRF2), a major regulator of the antioxidant response. Both UVA-1 irradiation and treatment with oxidized lipids led to increased nuclear accumulation and DNA binding of NRF2. Silencing and deficiency of NRF2 suppressed the antioxidant response. Taken together, our data show that UVA-1-mediated lipid oxidation induces expression of antioxidant response genes, which is dependent on the redox-regulated transcription factor NRF2. Our findings suggest a different view on UV-generated lipid mediators that were commonly regarded as detrimental
|
| 巻・号 |
24(1)
|
| ページ |
39-48
|
| 公開日 |
2010-1-1
|
| DOI |
10.1096/fj.09-133520
|
| PII |
fj.09-133520
|
| PMID |
19720622
|
| PMC |
PMC2797031
|
| MeSH |
Animals
Antioxidants / metabolism
Base Sequence
Cells, Cultured
Fibroblasts / metabolism
Fibroblasts / radiation effects
Gene Expression / radiation effects
Glutamate-Cysteine Ligase / biosynthesis
Heme Oxygenase-1 / biosynthesis
Humans
Keratinocytes / metabolism
Keratinocytes / radiation effects
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Multigene Family / radiation effects
NF-E2-Related Factor 2 / antagonists & inhibitors
NF-E2-Related Factor 2 / deficiency
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism*
Oxidation-Reduction
Oxidative Stress / radiation effects
Phospholipids / metabolism*
Phospholipids / radiation effects*
Promoter Regions, Genetic
RNA, Small Interfering / genetics
Skin / cytology
Skin / metabolism*
Skin / radiation effects*
Ultraviolet Rays
|
| IF |
4.966
|
| 引用数 |
56
|
|
WOS 分野
|
BIOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01390 |
