Study of atorvastatin induced ferroptosis in MIN6 cells and its related mechanisms
CSTR:
Author:
Affiliation:

Department of Endocrinology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029 ,China

Clc Number:

Fund Project:

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    Objective:To explore whether atorvastatin(Ator)can induce ferroptosis in pancreatic β- cell line MIN6 cells and its possible mechanism. Methods:MIN6 cells were divided into control group,Ator group,Ator+apoptosis inhibitor(Z-VAD-FMK)group, Ator+necrostatin-1(Nec-1)group and Ator+ferrostatin-1(Fer-1)group. Cell viability was detected by cell counting kit-8(CCK-8) method. The ultrastructure of cells was observed by transmission electron microscopy. The levels of reactive oxygen species(ROS)and Fe2+ were observed by fluorescence microscopy. The contents of malondialdehyde(MDA)and glutathione(GSH)were detected by enzyme-linked immunosorbent assay(ELISA)method. Real-time quantitative PCR was used to detect the mRNA levels of caspase-3, receptor-interacting protein kinase 3(Ripk3),acyl-CoA synthetase long-chain family member 4(Acsl4),prostaglandin endoperoxidase synthase 2(Ptgs2)and glutathione peroxidase 4(Gpx4). Western blot was used to detect the proteins levels of 4-hydroxynonenal (4-HNE)and GPX4. Results:Compared with the Ator group,cell viability of MIN6 was higher in Ator+Z-VAD-FMK group and Ator+ Fer -1 group(P < 0.01). MIN6 cells,which were treated with Ator,exhibited the characteristic morphologic features associated with apoptosis,ferroptosis and autophagy under transmission electron microscopy. Compared with the control group,the levels of the intracellular Fe2+ ,MDA and ROS in the Ator group were increased and GSH was decreased. The mRNA relative expression levels of caspase-3,Acsl4 and Ptgs2 were increased,as well as the protein relative expression level of 4-HNE(all P < 0.05). The mRNA and protein relative expression levels of GPX4 were decreased(P < 0.05). Compared with the Ator group,the levels of the intracellular Fe2+ ,MDA and ROS in the Ator+Fer-1 group were decreased and GSH was increased. The mRNA relative expression level of Acsl4 was decreased and Gpx4 was increased(all P < 0.05). The protein relative expression levels of 4-HNE was decreased and GPX4 was increased,though the changes were not statistically significant. Conclusion:Atorvastatin may induce ferroptosis in MIN6 cells by down-regulating GPX4 expression through inhibiting mevalonate pathway.

    Reference
    Related
    Cited by
Get Citation

魏倩影,陈欣,秦瑶,李雨潇,秦璐,张梅.阿托伐他汀诱导的MIN6细胞铁死亡及相关机制研究[J].南京医科大学学报(自然科学版英文版),2024,(8):1044-1050.

Copy
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
History
  • Received:March 04,2024
  • Revised:
  • Adopted:
  • Online: August 09,2024
  • Published:
Article QR Code