Role of oxidative stress and mitochondrial changes in cyanobacteria-induced apoptosis and hepatotoxicity.
Microcystins produced by cyanobacteria are potent and specific hepatotoxins; however, the mechanisms of microcystin-induced hepatotoxicity have not been fully elucidated. The induction of free radical formation and mitochondrial alterations are two major events found in microcystin-treated cultured rat hepatocytes. The mitochondrial alterations, i.e. loss of mitochondrial membrane potential and mitochondria permeability transition are now recognized as key steps in apoptosis. The activation of calpain and Ca(2+)/calmodulin-dependent protein kinase II is believed to be critical in the microcystin-induced apoptotic process.
Ding
Wen-Xing
WX
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. wed1@pitt.edu
Nam Ong
Choon
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000382:microbiology; D000458:Cyanobacteria / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology; D008954:Models, Biological; D015394:Molecular Structure; D018384:Oxidative Stress; D010456:Peptides, Cyclic / Q000009:adverse effects* / Q000494:pharmacology; D010539:Permeability; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002154:Calpain; D020169:Caspases; C057862:cyanoginosin LR