Evaluation of sphingolipid metabolism in renal cortex of rats with streptozotocin-induced diabetes and the effects of rapamycin.
BACKGROUND
Abnormal lipid metabolism contributes to the pathogenesis of diabetes, but it is uncertain whether it plays a role in the development of diabetic nephropathy (DN). While rapamycin was shown to prevent DN development in streptozotocin (STZ)-induced diabetic rats in our previous studies, it is unknown if it intervenes with lipid metabolism.


METHODS
We divided the rats into four groups: normal control rats, rapamycin-treated normal rats, diabetic rats and rapamycin-treated DN rats. The apoptosis was evaluated by immunohistochemistry. The crude lipid and sphingolipid were extracted from rat renal cortex and analysed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The expression of the three key enzymes in sphingolipid metabolism including serine palmitoyltransferase, acid sphingomyelinase and sphingomyelin synthase was measured by western blot and immunohistochemistry in rat renal cortex.


RESULTS
The level of apoptosis was increased in diabetic rats, and rapamycin treatment reduced apoptosis. STZ treatment significantly increased formation of many sphingolipids species through elevated de novo synthesis. These changes were inhibited by treatment with rapamycin.


CONCLUSIONS
Accumulation of sphingolipids contributes to STZ-induced diabetes, and the therapeutic effect of rapamycin on diabetic nephropathy is partly through suppression of sphingolipid abnormality.
Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
GuangYi
G
Liu
Fei
F
Han
Yi
Y
Yang
Yi
Y
Xie
Hong
H
Jiang
YouYing
Y
Mao
HuiPing
H
Wang
MinMin
M
Wang
RongJun
R
Chen
Jun
J
Yang
JiangHua
J
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013107:Sphingolipids / Q000378:metabolism*; D013311:Streptozocin
D007166:Immunosuppressive Agents; D013107:Sphingolipids; D013311:Streptozocin; D020123:Sirolimus