The p53-mediated apoptosis in hypercholesterolemia-induced renal injury of rats.
The apoptosis and the expression of tumor suppressor gene p53 in hypercholesterolemia (HC)-induced renal injury were investigated in rats. A high cholesterol diet (HCD)-induced HC rat model was made and serum lipid, urinary protein excretion (UPE) and N-aceto-beta-D-glucosidase (NAG) were measured. The levels of malondialdehyde (MDA), as an index of lipid peroxidation, in renal cortex and serum were compared between the two diet groups. Apoptosis and p53 expression were determined by TUNEL and immunohistochemistry, respectively. In the HCD-induced HC group, serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) as well as triglyceride (TG) were significantly increased, while the level of high density lipoprotein-cholesterol (HDL-C) decreased. Meanwhile, increased excretions of UPE and NAG in urine were observed, which were accompanied with a decrease in urinary creatinine clearance (Ccr) and indicated both glomerular and tubular damages. In addition, apoptotic cell death coexisted in the kidney, as revealed by increased TUNEL positive cells. Finally, an increase in p53 expression was observed in tubuli, but not in glomeruli. Both TUNEL, positive cells and p53 expression were found to be correlated to the level of renal cortical MDA (r = 0.817, P < 0.01 and r = 0.547, P < 0.01, respectively). The major manifestation of HCD-induced renal injury is apoptosis. The lipid peroxidation is a critical event to induce DNA damage and p53 is involved in the pathogenesis of lipid-induced renal injury.
Yao
Ying
Y
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Tian
Xingkui
X
Liu
Xiaocheng
X
Shao
Jufang
J
Lv
Yongman
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D004041:Dietary Fats; D016159:Tumor Suppressor Protein p53