La3+, Gd3+ and Yb3+ 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 NIT and reactive oxygen species (ROS) in Ln-induced apoptosis. We found that micromolar or lower concentration of La3+, Gd3+ and Yb3+ bound to NIT and induced swelling of isolated MT; EGTA treatment can inhibit the process. In addition, La3+, Gd3+ and Yb3+ increased the NIT membrane fluidity and decreased the NIT 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 NIT pathways and it was highly possible that ROS were involved in the mechanism. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.Biochemistry & Molecular BiologyPharmacology & PharmacyToxicologySCI(E)PubMed52ARTICLE127-3714