Molecular events involved in ochratoxin A induced mitochondrial pathway of apoptosis, modulation by Bcl-2 family members.
In this study, we looked for the role of the mitochondrion in the cytotoxicity of ochratoxin A (OTA), which is one of the most abundant food-contaminating mycotoxins in the world. In different human carcinoma cell lines, OTA triggered a mitochondria-dependent apoptotic process, which is characterized by opening of the mitochondrial permeability transition pore (PTPC), loss of mitochondrial transmembrane potential (ΔΨ(m) ), increase in O(2) [chemp](-) production, mitochondrial relocalization of Bax, release of cytochrome c, and caspase activation. However, studies performed on purified organelles suggested that OTA does not directly target the mitochondrion. In addition, we showed that mitochondrial alterations induced by this mycotoxin are favored by the proapoptotic protein Bax, but not Bak. These alterations are prevented by the antiapoptotic proteins, Bcl-2 and to a lesser degree by Bcl-X(L). Taken together, these data indicate that although mitochondria, PTPC members and proteins of Bcl-2 family play a pivotal role in OTA-induced apoptosis, they do not constitute real targets to overcome its toxicity.
Bouaziz
Chayma
C
Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, Monastir 5000, Tunisia.
Sharaf el dein
Ossama
O
Martel
Cécile
C
El Golli
Emna
E
Abid-Essefi
Salwa
S
Brenner
Catherine
C
Lemaire
Christophe
C
Bacha
Hassen
H
D017209:Apoptosis / Q000502:physiology; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009793:Ochratoxins / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D002273:Carcinogens; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009793:Ochratoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C025589:ochratoxin A; D045304:Cytochromes c