Full
Outline
To explore the role and mechanism of ferroptosis in vitamin D3 (VD3) improving the cytotoxicity of keratinocytes (HaCaT cells) induced by nitrogen mustard (NM).
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.
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.
VD3 mitigates NM-induced cytotoxicity in HaCaT cells by inhibiting ferroptosis via Nrf2 activation.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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