Mechanism of Methylglyoxal via Srebp-1/Gpx4 to Enhance the Sensitivity of Tubular Epithelial Cells to Ferroptosis in Inducing Lipotoxicity-A Proposal Using Nad+ for Treatment

Project: A - Government Institution › b - National Science and Technology Council

Project Details

Description

葡萄糖可自行被氧化形成MG代謝產物,需仰賴消耗GSH的GLO-1代謝,然高血糖病患因glyoxalase系統功能低下,以致羰基壓力增加,當細胞面臨壓力,細胞內可能因應環境需求生成脂滴提供保護.之前研究結果顯示腎小管細胞在MG作用時,產生脂滴,也產生腎脂毒性.由於GSH不足與鐵死亡及羰基壓力皆有關,但迄今未有於腎小管細胞探討MG與細胞鐵死亡的研究,且NAMPT可提升細胞NAD+,增強Glutathione的合成.因此本計畫擬先釐清MG作用下,脂質代謝與鐵死亡的相關性及訊息調控路徑並嘗試由NAMPT調控路徑了解其與MG/脂質堆積/鐵死亡關聯,雙管齊下針對羰基壓力和脂質氧化壓力找尋新的糖尿腎臟病治療
StatusFinished
Effective start/end date8/1/23 → 7/31/24

Keywords

  • Ferroptosis
  • Methylglyoxal (MG)
  • Sterol regulatory element-binding protein 1 (SREBP1)
  • Glutathione peroxidase 4 (GPX4)
  • gluthione (GSH)
  • Nicotinamide adenine dinucleotide ( NAD+)