| RRC ID |
72672
|
| 著者 |
Niu J, Wan X, Yu GY, Jiang S, Yi RN, Wu YP, Ouyang SH, Liang L, Kurihara H, Sun WY, Zhu XF, Zhang RH, Cao YF, He JB, Duan WJ, Li YF, He RR.
|
| タイトル |
Phospholipid peroxidation-driven modification of chondrogenic transcription factor mediates alkoxyl radicals-induced impairment of embryonic bone development.
|
| ジャーナル |
Redox Biol
|
| Abstract |
Maternal stress has been associated with poor birth outcomes, including preterm birth, infant mortality, and low birth weight. Bone development disorders in the embryo as a result of maternal stress are believed to be mediated through oxidative stress damage. Various species of free radicals, such as alkoxyl radicals, can be formed through endogenous redox response or exogenous stimuli in the womb and transmitted to embryos. Yet, whether these free radicals lead to abnormal fetal bone development is unclear. Here, we demonstrate prenatal bone growth retardation and ferroptosis-related signals of chondrocytes were induced by classic alkoxyl radical generators. We also show that alkoxyl radicals lead to significant accumulation of oxidized phospholipids in chondrocytes, through the iron-mediated Fenton reaction in embryos. We further demonstrate a role for the lipid peroxidation end product, 4-HNE, which forms adducts with the pivotal chondrogenesis transcription factor SOX9, leading to its degradation, therefore dampening chondrogenesis. Our data define a critical role for phospholipid peroxidation in alkoxyl radicals-evoked abnormal chondrogenesis, and pinpoint it being a precise target for treating oxidative stress-related bone development disorders.
|
| 巻・号 |
56
|
| ページ |
102437
|
| 公開日 |
2022-10-1
|
| DOI |
10.1016/j.redox.2022.102437
|
| PII |
S2213-2317(22)00209-9
|
| PMID |
36037588
|
| PMC |
PMC9440361
|
| MeSH |
Alcohols
Bone Development
Chondrogenesis
Female
Free Radicals / metabolism
Humans
Infant, Newborn
Iron
Lipid Peroxidation
Phospholipids* / metabolism
Premature Birth*
Transcription Factors / metabolism
|
| IF |
9.986
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
