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Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre

Electronic Theses and Dissertations

Acute kidney injury (AKI), resulting from cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves cell death pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results indicate that cisplatin-treated mice had increased levels of ceramide and hexosylceramide. Pre-treatment of mice with inhibitors of ceramide synthesis prevented accumulation of ceramide and hexosylceramide in the renal cortex and attenuated cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with an inhibitor of glycosphingolipid synthesis. Inhibition of glycosphingolipid synthesis attenuated the accumulation of the hexosylceramide and exacerbated ceramide accumulation in the …