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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
The cyanobacterial toxin, microcystin-LR, can induce apoptosis in a variety of cell types
C M McDermott1, C W Nho, W Howard
1Department of Biology and Microbiology, Halsey Science Center, University of Wisconsin Oshkosh, 54901, USA.
Abstract:
Cyanobacterial toxins, especially the microcystins (MCYST), are found in eutrophied waters throughout the world. These toxins cause hepatocyte damage by inhibiting protein phosphatases 1 and 2A, resulting in hyperphosphorylation of cytoskeletal proteins. Acute intoxication of animals and humans has been reported following MCYST exposure. Okadaic acid, a marine biotoxin, has a similar mechanism of action to MCYST and has been shown to cause apoptosis, a form of programmed cell death, in a variety of cell types. In this study, primary rat hepatocytes (in suspension and monolayer culture), human fibroblasts, human endothelial cells, human epithelial cells, and rat promyelocytes were observed following treatment with MCYST for morphological and biochemical changes typical of apoptosis. Hepatocytes underwent cell membrane blebbing, cell shrinkage, organelle redistribution, and chromatin condensation as early as 30 min following MCYST application (0.8 microM). Other cell types treated with MCYST (100 microM) also showed these morphological changes, but required a longer period of treatment. DNA fragmentation and "ladder" formation occurred in most cell types exposed to MCYST. These observations demonstrate that MCYST causes apoptosis in a variety of mammalian cells.
Insights
Microcystins (MCYST), harmful cyanobacterial toxins, induce apoptosis, programmed cell death, in various mammalian cells. This cellular damage occurs through specific morphological and biochemical changes following MCYST exposure.
Area of Science:
- Environmental Toxicology
- Cell Biology
- Biochemistry
Background:
- Cyanobacterial toxins, particularly microcystins (MCYST), are prevalent in eutrophied waters globally.
- MCYST inhibits protein phosphatases 1 and 2A, leading to hepatocyte damage via cytoskeletal protein hyperphosphorylation.
- Acute intoxication in humans and animals from MCYST exposure is a documented concern.
Purpose of the Study:
- To investigate the induction of apoptosis by microcystins (MCYST) in various mammalian cell types.
- To characterize the morphological and biochemical changes associated with MCYST-induced apoptosis.
Main Methods:
- Primary rat hepatocytes, human fibroblasts, human endothelial cells, human epithelial cells, and rat promyelocytes were utilized.
- Cells were treated with MCYST at varying concentrations (0.8 microM and 100 microM).
- Morphological changes (membrane blebbing, shrinkage, chromatin condensation) and biochemical markers (DNA fragmentation) of apoptosis were assessed.
Main Results:
- Hepatocytes exhibited early apoptotic changes within 30 minutes of MCYST exposure (0.8 microM).
- Other cell types demonstrated similar apoptotic morphology but required longer exposure times to MCYST (100 microM).
- DNA fragmentation and ladder formation, indicative of apoptosis, were observed in most MCYST-treated cell types.
Conclusions:
- Microcystins (MCYST) induce apoptosis in a diverse range of mammalian cell types.
- MCYST triggers characteristic morphological and biochemical hallmarks of programmed cell death.
- These findings highlight the cytotoxic potential of MCYST beyond hepatocyte damage.
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