University of Illinois Urbana-Champaign

Toxicity of microcystin-LR in hepatocytes and non-hepatocytes in vitro

Khan, Safdar Ali

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Description

Title
Toxicity of microcystin-LR in hepatocytes and non-hepatocytes in vitro
Author(s)
Khan, Safdar Ali
Issue Date
1994
Doctoral Committee Chair(s)
Beasley, Val Richard
Department of Study
Veterinary Medicine
Discipline
Pathobiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
  • Agriculture, Animal Pathology
  • Health Sciences, Pathology
  • Biology, Veterinary Science
Language
eng
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.
Type of Resource
text
Permalink
http://hdl.handle.net/2142/21679
Copyright and License Information
Copyright 1994 Khan, Safdar Ali

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