Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2
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 f...
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Editorial Office of Journal of Army Medical University
2025-04-01
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| Series: | 陆军军医大学学报 |
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| Online Access: | https://aammt.tmmu.edu.cn/html/202409076.html |
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| _version_ | 1850184195173777408 |
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| author | DONG Xunhu LIU Haoyin GE Wei |
| author_facet | DONG Xunhu LIU Haoyin GE Wei |
| author_sort | DONG Xunhu |
| collection | DOAJ |
| description | 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.
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| format | Article |
| id | doaj-art-51540878ce7845b59f4584d736c6c754 |
| institution | OA Journals |
| issn | 2097-0927 |
| language | zho |
| publishDate | 2025-04-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj-art-51540878ce7845b59f4584d736c6c7542025-08-20T02:17:06ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272025-04-0147767468010.16016/j.2097-0927.202409076Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2DONG Xunhu0LIU Haoyin1GE Wei2Department of Chemical Defense, Faculty of Military Preventive Medicine， Army Medical University （Third Military Medical University）， Chongqing， ChinaDepartment of Chemical Defense, Faculty of Military Preventive Medicine， Army Medical University （Third Military Medical University）， Chongqing， ChinaDepartment of Chemical Defense, Faculty of Military Preventive Medicine， Army Medical University （Third Military Medical University）， Chongqing， ChinaObjective 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. https://aammt.tmmu.edu.cn/html/202409076.htmlnitrogen mustardvitamin d3nuclear factor e2 related factor 2keratinocytesferroptosis |
| spellingShingle | DONG Xunhu LIU Haoyin GE Wei Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2 陆军军医大学学报 nitrogen mustard vitamin d3 nuclear factor e2 related factor 2 keratinocytes ferroptosis |
| title | Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2 |
| title_full | Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2 |
| title_fullStr | Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2 |
| title_full_unstemmed | Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2 |
| title_short | Vitamin D3 inhibits nitrogen mustard-induced keratinocyte ferroptosis by activating Nrf2 |
| title_sort | vitamin d3 inhibits nitrogen mustard induced keratinocyte ferroptosis by activating nrf2 |
| topic | nitrogen mustard vitamin d3 nuclear factor e2 related factor 2 keratinocytes ferroptosis |
| url | https://aammt.tmmu.edu.cn/html/202409076.html |
| work_keys_str_mv | AT dongxunhu vitamind3inhibitsnitrogenmustardinducedkeratinocyteferroptosisbyactivatingnrf2 AT liuhaoyin vitamind3inhibitsnitrogenmustardinducedkeratinocyteferroptosisbyactivatingnrf2 AT gewei vitamind3inhibitsnitrogenmustardinducedkeratinocyteferroptosisbyactivatingnrf2 |