A-485 alleviates tubular lipid accumulation by inhibiting H3K18ac/H3K27ac induced by P300/CBP in diabetic mice
10.13315/j.cnki.cjcep.2024.05.012
- VernacularTitle:A-485 通过抑制 P300/CBP 诱导的 H3K18ac/H3K27ac减轻糖尿病肾小管细胞脂质沉积
- Author:
Li MENG
1
;
Yan ZHU
;
Yan YANG
;
Ting WU
;
Yunzhuo REN
;
Linshan DU
;
Shijie ZENG
;
Chunyang DU
Author Information
1. 河北医科大学电镜实验中心,石家庄 050017
- Keywords:
diabetic kidney disease;
P300/CBP;
A-485;
lipid accumulation;
acetylation
- From:
Chinese Journal of Clinical and Experimental Pathology
2024;40(5):509-514
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the protective effect and mechanism of A-485 on renal tubular injury in diabetic mice.Methods Eighteen male C57BL/6J mice were randomly divided into three groups:Control group,diabetic kidney dis-ease(DKD)group and A-485 treatment group.The DKD mice model was established by feeding high-fat diet for 8 weeks and intraperitoneal injection of streptozotocin for 5 days.Subsequent-ly,the A-485 treatment group was given A-485(10 mg/kg/day)by intraperitoneal injection every other day for 4 weeks.After treatment,the renal function,P300 enzyme activity and lipid deposition in renal tissue were measured.Western blot a-nalysis was performed to detect SREBP-1,FASN,ACC,ChREBP,P300,CBP,H3K18ac and H3K27ac protein levels.Results Compared with control mice,the levels of FBG,BUN,Scr and UAE were significantly increased in diabetic mice(FBG:2.52 times,BUN:2.89 times,Scr:2.13 times,UAE:4.21 times),while diabetic mice treatment with A-485 exhibi-ted a remarkable decrease on BUN,Scr and UAE(BUN:0.511 times,Scr:0.636 times,UAE:0.574 times,P＜0.01).The results of the transmission electron microscopy and oil red O stai-ning showed that A-485 treatment prevents lipid droplets forma-tion and up-regulation of SREBP-1,FASN,ACC and ChREBP in renal tubular cells of diabetic mice(SREBP-1:0.544 times,FASN:0.449 times,ACC:0.306 times,ChREBP:0.317 times,P＜0.01).Furthermore,A-485 intervention downregu-lated the enzyme activity of P300(0.546 times)and suppressed the expression of H3K18ac(0.337 times)and H3K27ac(0.308 times,P＜0.01).Conclusion A-485 can significant-ly improve renal lipid metabolic disorder in diabetic mice,which may be achieved by inhibiting p300-induced H3K18ac and H3K27ac.
