Acrolein-induced Neuronal Ferroptosis in Vitro and in Vivo： A Preliminary Study
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0503
- VernacularTitle:丙烯醛体内外诱导神经元铁死亡的初步研究
- Author:
Wei-jia PENG
1
;
Ze-yu ZHU
1
;
Yang YANG
2
;
Jia-wei HOU
2
;
Rong-biao PI
2
Author Information
1. Department of Pharmacology & Toxicology， School of Pharmaceutical Sciences， Sun Yat-sen University， Guangzhou 510006， China
2. Department of Pharmacology， School of Medicine，Sun Yat-sen University， Shenzhen 518107， China
- Publication Type:Journal Article
- Keywords:
Acrolein;
ferroptosis;
lipid peroxidation;
iron homeostasis;
Alzheimer's disease
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(5):659-666
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore whether acrolein can induce ferroptosis in vitro and in vivo. MethodsHT22 cells were treated with acrolein and then incubated with ferroptosis inhibitor ferrostatin-1 （Fer-1） and deferoxamine （DFO）. MTT assay was used to detect the cell survival rate. Dihydroethidium （DHE） and FerroOrange probes were used to detect the contents of free radicals and ferrous ions in cells. A transmission electron microscope observed the structure of mitochondria in standard and acrolein groups. Western blot was used to detect the levels of ferroptosis-related proteins GPX4， COX-2， and FTH1 in vitro. In vivo， male C57BL/6 mice were given 3 mg/kg acrolein every day at the age of 7-8 weeks for 1， 2， and 4 weeks， and the levels of ferroptosis-related proteins GPX4， COX-2， and FTH1 in the hippocampus was detected by western blot. ResultsAcrolein significantly reduced the survival rate of HT22 cells and induced mitochondrial shrinkage， and decreased the number of cristae. Meanwhile， acrolein could remarkably increase intracellular free radical and ferrous ions. In addition， acrolein promoted the increase in the expression of Cyclooxygenase-2 （COX-2） and Ferritin Heavy Chain 1 （FTH1） at the cellular level and decreased the expression of Glutathione peroxidase 4 （GPX4）. At the animal level， acrolein promoted the increase of COX-2 expression and decreased the expressions of GPX4 and FTH1. ConclusionAcrolein induced neuronal ferroptosis in vitro and in vivo， suggesting ferroptosis inhibitors could attenuate acrolein-associated diseases in CNS， such as Alzheimer's disease.
