Abstract
Nephrotoxicity is one of critical problems of aminoglycoside antibiotics. We examined the protective effect of apolipoprotein E3 (apoE3), one of ligands for megalin, on neomycin-induced extracellular release of lactate dehydrogenase, a marker of cell necrosis using pig proximal tubular LLC-PK1 cells. Neomycin significantly induced the extracellular release of lactate dehydrogenase, but apoE3 successfully suppressed it. This result indicated that apoE3 protects the proximal tubular cells from the eventual cell death induced by nephrotoxic aminoglycosides.
Similar content being viewed by others
Article PDF
References
Schmitz C, Hilpert J, Jacobsen C, Boensch C, Christensen EI, Luft FC, Willnow TE . Megalin deficiency offers protection from renal aminoglycoside accumulation. J Biol Chem 277: 618–622 ( 2002)
Nagai J, Tanaka H, Nakanishi N, Murakami T, Takano M . Role of megalin in renal handling of aminoglycosides. Am J Physiol Renal Physiol 281: F337–F344 ( 2001)
Takamoto K, Kawada M, Ikeda D, Yoshida M . Apolipoprotein E3 (apoE3) safeguards pig proximal tubular LLC-PK1 cells against reduction in SGLT1 activity induced by gentamicin C. Biochim Biophys Acta 1722: 247–253 ( 2005)
Kaloyanides GJ, Pastriza-Munoz E . Aminoglycoside nephrotoxicity. Kidney Int 18: 571–582 ( 1980)
Takamoto K, Kawada M, Usui T, Ikeda D, Ishizuka M, Takeuchi T . Inhibitory activity of dome formation in LLC-PK1 cells is a selective index of aminoglycoside nephrotoxicity. J Antibiot 55: 605–606 ( 2002)
Girton RA, Sundin DP, Rosenberg ME . Clusterin protects renal tubular epithelial cells from gentamicin-mediated cytotoxicity. Am J Physiol Renal Physiol 282: F703–F709 ( 2002)
Blais A, Morvan-Baleynaud J, Friedlander G, Le Grimellec C . Primary culture of rabbit proximal tubules as a cellular model to study nephrotoxicity of xenobiotics. Kidney Int 44: 13–18 ( 1993)
Kounnas MZ, Loukinova EB, Stefansson S, Harmony JAK, Brewer BH, Strickland DK, Argraves WS . Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. J Biol Chem 270: 13070–13075 ( 1995)
Birn H, Fyte JC, Jacobsen C, Mounier F, Verroust PJ, Ørskov H, Willnow TE, Moestrup SK, Christensen EI . Cubilin is an albumin binding protein important for renal tubular albumin reabsorption. J Clin Invest 105: 1353–1361 ( 2000)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takamoto, K., Kawada, M. & Ikeda, D. Prevention of Neomycin-induced Nephrotoxic Event in Pig Proximal Tubular Epithelial Cell Line by Apolipoprotein E3. J Antibiot 58, 353–355 (2005). https://doi.org/10.1038/ja.2005.45
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ja.2005.45