Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2
10.16016/j.2097-0927.202409076
- VernacularTitle:维生素D3通过激活Nrf2抑制氮芥诱导角质形成细胞铁死亡的作用研究
- Author:
Xunhu DONG
1
;
Haoyin LIU
;
Wei GE
;
Mingliang CHEN
Author Information
1. 陆军军医大学(第三军医大学)军事预防医学系防化医学教研室
- Keywords:
nitrogen mustard;
vitamin D3;
nuclear factor E2 related factor 2;
keratinocytes;
ferroptosis
- From:
Journal of Army Medical University
2025;47(7):674-680
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role and mechanism of ferroptosis in vitamin D3(VD3)improving the cytotoxicity of keratinocytes(HaCaT cells)induced by nitrogen mustard(NM).Methods HaCaT cells were treated with gradient concentrations of NM(5,10,20,and 50 μmol/L)alone or in combination with ferroptosis inhibitor ferrostatin-1 or liproxstatin-1(10 μmol/L),Nrf2-specific agonist tBHQ(10 μmol/L),and VD3(10 nmol/L),respectively.After co-culture for 24 h,cell viability was assessed,and the intracellular contents of glutathione(GSH)and malondialdehyde(MDA)were measured.Additionally,the expression levels of Nrf2,xCT,and GPX4 were detected.Results NM exerted inhibitory effect on the proliferation of HaCaT cells in a dose-dependent manner,and the cell viability was reduced to approximately 55%at an NM concentration of 20 μmol/L(P<0.05).Ferroptosis inhibitors significantly mitigated the cytotoxic damage induced by NM in HaCaT cells(P<0.05),but activation of nuclear factor E2 related factor 2(Nrf2)markedly attenuated NM-induced ferroptosis,as indicated by the restoration of intracellular GSH level and the decrease in MDA content(P<0.05).VD3 specifically targeted the Nrf2 signaling pathway,upregulated the expression of xCT and GPX4 protein,thereby inhibiting ferroptosis and reducing NM-induced cytotoxicity in HaCaT cells.Conclusion VD3 mitigates NM-induced cytotoxicity in HaCaT cells by inhibiting ferroptosis via Nrf2 activation.
