Morace, Ivan and Pilz, Robert and Federico, Giuseppina and Jennemann, Richard and Krunic, Damir and Nordstroem, Viola and von Gerichten, Johanna and Marsching, Christian and Schiessl, Ina Maria and Muething, Johannes and Wunder, Christian and Johannes, Ludger and Sandhoff, Roger and Groene, Hermann-Josef (2019) Renal globotriaosylceramide facilitates tubular albumin absorption and its inhibition protects against acute kidney injury. KIDNEY INTERNATIONAL, 96 (2). pp. 327-341. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)Abstract
To elucidate the physiologic function of renal globotriaosylceramide (Gb3/CD77), which up-to-date has been associated exclusively with Shiga toxin binding, we have analyzed renal function in Gb3-deficient mice. Gb3 synthase KO (Gb3S(-/-)) mice displayed an increased renal albumin and low molecular weight protein excretion compared to WT. Gb3 localized at the brush border and within vesicular structures in WT proximal tubules and has now been shown to be closely associated with the receptor complex megalin/cubilin and with albumin uptake. In two clinically relevant mouse models of acute kidney injury caused by myoglobin as seen in rhabdomyolysis and the aminoglycoside gentamicin, Gb3S(-/-) mice showed a preserved renal function and morphology, compared to WT. Pharmacologic inhibition of glucosylceramide-based glycosphingolipids, including Gb3, in WT mice corroborated the results of genetically Gb3-deficient mice. In conclusion, our data significantly advance the current knowledge on the physiologic and pathophysiologic role of Gb3 in proximal tubules, showing an involvement in the reabsorption of filtered albumin, myoglobin and the aminoglycoside gentamicin.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROXIMAL TUBULE; SHIGA TOXIN; CERAMIDE; MEGALIN; CELLS; NEPHROTOXICITY; ENDOCYTOSIS; BLOCKADE; CUBILIN; MICE; acute kidney injury; endocytosis; gentamicin; globotriaosylceramide; rhabdomyolysis |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 08:37 |
| Last Modified: | 01 Apr 2020 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26566 |
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