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Title:Toxicity of microcystin-LR in hepatocytes and non-hepatocytes in vitro
Author(s):Khan, Safdar Ali
Doctoral Committee Chair(s):Beasley, Val Richard
Department / Program:Veterinary Medicine
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Agriculture, Animal Pathology
Health Sciences, Pathology
Biology, Veterinary Science
Abstract:Microystin-LR (MCLR), a cyanobacterial heptapeptide is an inhibitor of protein phosphatases 1 and 2A (PPs), a potential tumor promoter in rat liver, and selectively toxic to the liver in vivo and isolated hepatocytes in vitro. Inhibition of PPs has been linked to excessive phosphorylation and collapse of intermediate filaments (IFs) in hepatocytes. MCLR was used as a probe to understand the mechanism of action of this toxin in hepatocytes and non-hepatocytes.
Cultured rat skin fibroblasts and rat kidney epithelial cells were incubated with MCLR at 133 pM for 1 to 24 hr. Pathologic changes, or cytoskeletal changes in IFs, microtubules (MTs), and microfilaments (MFs) at the light and ultrastructural levels in these cells were compared with those in cultured hepatocytes incubated with MCLR at 13.3, 1.3, or 0.13 pM from 1 to 32 min. Changes in a 58 kDa microtubule associated protein, MTs, and IFs in hepatocytes incubated with MCLR at 13.3, 1.3, or 0.13 pM were characterized. Lesions in all three cell types included: plasma membrane blebbing, loss of cell-to-cell contact, clumping and rounding of cells, cytoplasmic vacuolization, and redistribution of cytoplasmic organelles. Loss of microvilli, whorling of rough endoplasmic reticulum, dense staining and dilated cristae in mitochondria, and pinching off of membrane blebs were noted only in hepatocytes. Nuclear changes typical of apoptosis were observed only in fibroblasts and kidney cells.
Issue Date:1994
Rights Information:Copyright 1994 Khan, Safdar Ali
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9503231
OCLC Identifier:(UMI)AAI9503231

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