Journal article

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

Abstract

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