Abstract

Cystamine has been shown to alter intracellular Ca2+ homeostasis in isolated perfused rat liver and isolated hepatocytes by inhibiting Ca2+ efflux. This inhibition of the active extrusion of Ca2+ from hepatocytes is associated with the formation of mixed disulfides between cystamine and plasma membrane thiols and a subsequent inactivation of Ca2+-ATPase. The resulting sustained increase in cytosolic free Ca2+ is followed by both proteolysis and phospholipid hydrolysis, the proposed mechanism of hepatotoxicity.We have investigated cystamine-induced nephrotoxicity in PTC primary cultures. This study reports ultrastructural changes in kidney cells resulting from exposure to 10 mM cystamine for 15, 60, 120 and 180 min.Primary tubular cells were isolated from male Fischer 344 rat kidney cortex and maintained in a 50:50 mixture of DME and Ham's F12. Four day-old cultures were treated with cystamine, washed twice with HBSS, fixed in 4% phosphate-buffered formaldehyde:1% glutaraldehyde, post-fixed is OsO4, dehydrated through an ethanol series and embedded in Polybed 812. Ultrathin sections were examined in a JEOL 100B electron microscope.

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