Sphingolipid imbalance and inflammatory effects induced by uremic toxins in heart and kidney cells are reversed by dihydroceramide desaturase 1 inhibition
Feby Savira, Ruth Magaye, Carmen Scullino, Bernard L Flynn, Stuart M Pitson, Dovile Anderson, Darren J Creek, Yue Hua, Xin Xiong, Li Huang, Danny Liew, Christopher Reid, David Kaye, Andrew R Kompa, Bing Hui Wang
TOXICOLOGY LETTERS | ELSEVIER IRELAND LTD | Published : 2021
Non-dialysable protein-bound uremic toxins (PBUTs) contribute to the development of cardiovascular disease (CVD) in chronic kidney disease (CKD) and vice versa. PBUTs have been shown to alter sphingolipid imbalance. Dihydroceramide desaturase 1 (Des1) is an important gatekeeper enzyme which controls the non-reversible conversion of sphingolipids, dihydroceramide, into ceramide. The present study assessed the effect of Des1 inhibition on PBUT-induced cardiac and renal effects in vitro, using a selective Des1 inhibitor (CIN038). Des1 inhibition attenuated hypertrophy in neonatal rat cardiac myocytes and collagen synthesis in neonatal rat cardiac fibroblasts and renal mesangial cells induced by..View full abstract
Awarded by National Health and Medical Research Council of Australia
The work described here was funded by a National Health and Medical Research Council of Australia (Program Grant ID#1092642 and Project Grant ID#1087355) .