La(3+), Gd(3+) and Yb(3+) induced changes in mitochondrial structure, membrane permeability, cytochrome c release and intracellular ROS level.
Lanthanides (Ln) were known to induce cell apoptosis, which might be the results of their effects on mitochondria (MT). This study was trying to clarify the role of MT and reactive oxygen species (ROS) in Ln-induced apoptosis. We found that micromolar or lower concentration of La(3+), Gd(3+) and Yb(3+) bound to MT and induced swelling of isolated MT; EGTA treatment can inhibit the process. In addition, La(3+), Gd(3+) and Yb(3+) increased the MT membrane fluidity and decreased the MT membrane potential (DeltaPsi(m)). All these were inferred to the results of MT permeability transition pore opening. Release of cytochrome c (Cyt-c) from the MT upon incubation with Ln ions was monitored by immunocytochemistry, however, Cyt-c release was observed only in the cytosol of cells. In parallel with these events, there was a higher level of ROS found in the cells exposed to Ln. It was proposed that Ln-induced apoptosis via the MT pathways and it was highly possible that ROS were involved in the mechanism.
Liu
Huixue
H
Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Yuan
Lan
L
Yang
Xiaoda
X
Wang
Kui
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003574:Cytochrome c Group / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects; D028581:Lanthanoid Series Elements / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D003574:Cytochrome c Group; D007473:Ion Channels; D028581:Lanthanoid Series Elements; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species