Immunolocalization of Sphingolipid Catabolism Enzymes along the Nephron: Novel Early Urinary Biomarkers of Renal Damage

The objective of this study was to investigate whether the activity of enzymes involved in sphingolipid catabolism could be biomarkers to predict early renal damage in streptozotocin (STZ)-induced diabetic rats and Angiotensin II (Ang II)-induced hypertension rats. Diabetic and hypertensive rats had...

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Published in:International journal of molecular sciences 2023-12, Vol.24 (23), p.16633
Main Authors: Franco, Martha, Cano-Martínez, Agustina, Ramos-Godínez, María Del Pilar, López-Marure, Rebeca, Donis-Maturano, Luis, Sosa, José Santamaría, Bautista-Pérez, Rocio
Format: Article
Language:English
Subjects:
Animals
Aquaporins
Biological markers
Biomarkers
COVID-19
Creatinine
Dapagliflozin
Diabetes
Diabetes Mellitus, Experimental - metabolism
Disease transmission
Enzymes
Hypertension
Kidney - metabolism
Kidneys
Lipids
Localization
Metabolites
Mitochondria
Nephrons - metabolism
Plasma
Rats
Shear stress
Sphingolipids
Sphingomyelin Phosphodiesterase - metabolism
Sphingosine
Urine
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Summary:The objective of this study was to investigate whether the activity of enzymes involved in sphingolipid catabolism could be biomarkers to predict early renal damage in streptozotocin (STZ)-induced diabetic rats and Angiotensin II (Ang II)-induced hypertension rats. Diabetic and hypertensive rats had no changes in plasma creatinine concentration. However, transmission electron microscopy (TEM) analysis showed slight ultrastructural changes in the glomeruli and tubular epithelial cells from diabetic and hypertensive rats. Our results show that the acid sphingomyelinase (aSMase) and neutral sphingomyelinase (nSMase) activity increased in the urine of diabetic rats and decreased in hypertensive rats. Only neutral ceramidase (nCDase) activity increased in the urine of diabetic rats. Furthermore, the immunofluorescence demonstrated positive staining for the nSMase, nCDase, and sphingosine kinase (SphK1) in glomerular mesangial cells, proximal tubule, ascending thin limb of the loop of Henle, thick ascending limb of Henle's loop, and principal cells of the collecting duct in the kidney. In conclusion, our results suggest that aSMase and nCDase activity in urine could be a novel predictor of early slight ultrastructural changes in the nephron, aSMase and nCDase as glomerular injury biomarkers, and nSMase as a tubular injury biomarker in diabetic and hypertensive rats.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242316633