Duality of effect of La3+ on mitochondrial permeability transition pore depending on the concentration.
In order to explore the role of mitochondria in proliferation promotion and/or apoptosis induction of lanthanum, the mutual influences between La3+ and Ca2+ on mitochondrial permeability transition pore (PTP) opening were investigated with isolated mitochondria from rat liver. The experimental results revealed that La3+ influence the state of mitochondria in a concentration-dependent biphasic manner. La3+ in nanomolar concentrations, acting as a Ca2+ analog, entered mitochondrial matrix via the RuR sensitive Ca2+ channel and elevated ROS level, leading to opening of PTP indicated by mitochondrial swelling, reduction of ΔΨm and cytochrome c release. Inhibition of PTP with 10 μM CsA attenuated the effects of La3+. However, micromolar concentrations La3+ acted mainly as a Ca2+ antagonist, inhibiting PTP opening induced by Ca2+. We postulated that this action of La3+ on mitochondria through interaction with Ca2+ might be involved in the proliferation-promoting and apoptosis induction by La3?.
Dong
Shuai
S
Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, 100083 Beijing, China.
Zhao
Yuebin
Y
Liu
Huixue
H
Yang
Xiaoda
X
Wang
Kui
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007811:Lanthanum / Q000378:metabolism / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D012430:Ruthenium Red / Q000378:metabolism
D015220:Calcium Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D012430:Ruthenium Red; D007811:Lanthanum; D016572:Cyclosporine; D045304:Cytochromes c; D002118:Calcium