Membrane proteins are critical targets in free radical mediated cytolysis.
The hypothesis that proteins are critical targets in free radical mediated cytolysis was tested using U937 mononuclear phagocytes as targets and iron together with hydrogen peroxide to generate radicals. Those conditions which, after a lag of approx. 30 min, led to drastic lysis were also associated with very rapid membrane depolarisation. Conversely, when the early membrane depolarisation was prevented (by the addition of chelator and catalase), so was lysis. A similar correlation between early membrane depolarisation and subsequent lysis was also observed when the cells were exposed to a toxin from Actinobacillus actinomycetemcomitans. Those conditions of radical attack which led to lysis normally caused substantial lipid peroxidation. However, depolarisation and subsequent lysis were not prevented even when lipid peroxidation was completely suppressed by exogenous antioxidant. ATP levels were not grossly affected within the critical first 30 min period. These data exclude lipids and ATP as the target for lytic damage. We argue therefore that proteins are probably amongst the primary targets in cytolysis by radicals.
Richards
D M
DM
Cell Biology Research Group, Brunel University, Uxbridge, U.K.
Dean
R T
RT
Jessup
W
W
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity; D008054:Lipid Peroxides; D008264:Macrophages / Q000187:drug effects*; D008563:Membrane Lipids; D008564:Membrane Potentials; D008565:Membrane Proteins; D051379:Mice
D001427:Bacterial Toxins; D005609:Free Radicals; D008054:Lipid Peroxides; D008563:Membrane Lipids; D008565:Membrane Proteins; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D007501:Iron; D005978:Glutathione