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Am J Physiol Renal Physiol (August 21, 2002). doi:10.1152/ajprenal.00095.2002
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Articles in PresS, published online ahead of print August 21, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00095.2002
Submitted on March 12, 2002
Accepted on July 27, 2002

Nucleotide Depletion Increases Trafficking of Gentamicin to the Golgi Complex in LLC-PK1 Cells

Ruben M. Sandoval1, Robert L. Bacallao1, Kenneth W. Dunn2, Jeffrey D. Leiser2, and Bruce A. Molitoris1*

1 Departments of Medicine and Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush VA Medical Center, Indianapolis, IN, USA
2 Departments of Medicine and Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA

* To whom correspondence should be addressed. E-mail: bmolitor{at}iupui.edu.

Having shown rapid trafficking of aminoglycosides to the Golgi Complex in cell culture, we focused on the injurious interaction that occurs when gentamicin administration is preceded by renal ischemia. Using Texas Red labeled Gentamicin (TRG) as a tracer, we determined 15 minutes of cellular nucleotide depletion did not significantly increase subsequent uptake. However, cells previously depleted of nucleotides accumulated significantly more TRG within a dispersed Golgi Complex. Using Ricinnus communis and Lens culinaris lectins, which label specific compartments of the Golgi Complex, TGN/Trans and Medial/Cis compartments respectively, we determined the Medial/Cis compartment dispersed after 15 minutes of nucleotide depletion, yet the TGN/Trans compartment remained unaffected. An increase in the number of cells exhibiting disrupted Medial/Cis Golgi morphology following repletion in physiologic media containing gentamicin was also seen. In summary, the increase in nephrotoxicity seen when ischemia precedes aminoglycoside uptake may be part of a complex mechanism initially involving increased Golgi accumulation and prolonged Golgi dispersion. The Golgi complex must then endure the effects of gentamicin accumulated in larger quantities in an aberrant physiologic state.




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