Blocking mitochondrial permeability transition prevents p53 mitochondrial translocation during skin tumor promotion.
The tumor suppressor p53 can translocate into mitochondria and activate apoptosis. Here we studied whether p53 mitochondrial translocation and subsequent apoptosis were affected by blocking mitochondrial permeability transition pore using cyclosporine A (CsA) and bongkrekic acid (BA) in skin epidermal JB6 cells and skin tissues. Our results demonstrated that CsA and BA blocked TPA-induced p53 translocation, leading to protection against the loss of mitochondrial membrane potential and Complex I activity, and eventually suppression of apoptosis. Thus, our results suggest that mitochondrial permeability transition is required for p53 mitochondrial translocation.
Liu
Jianfeng
J
Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center, Shreveport, LA 71130, USA.
St Clair
Daret K
DK
Gu
Xin
X
Zhao
Yunfeng
Y
D000818:Animals; D001865:Bongkrekic Acid / Q000494:pharmacology; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D008811:Mice, Inbred DBA; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D001865:Bongkrekic Acid; D016572:Cyclosporine; D013755:Tetradecanoylphorbol Acetate