TY - JOUR
T1 - Resistance of mtDNA-depleted cells to apoptosis
AU - Ferraresi, Roberta
AU - Troiano, Leonarda
AU - Pinti, Marcello
AU - Roat, Erika
AU - Lugli, Enrico
AU - Quaglino, Daniela
AU - Taverna, Daniela
AU - Bellizzi, Dina
AU - Passarino, Giuseppe
AU - Cossarizza, Andrea
PY - 2008/6
Y1 - 2008/6
N2 - Cells lacking mitochondrial genome (defined as ρ0) are useful models in studies on cancer, aging, mitochondrial diseases and apoptosis, but several of their functional aspects have been poorly characterized. Using different clones of ρ0 cells derived from the human osteosarcoma line 143B, we have tested the effects of different apoptogenic molecules such as staurosporine (STS), doxorubicin, daunomycin and quercetin, and have analyzed apoptosis, mitochondrial membrane potential (MMP), levels of oxygen free radicals, reduced glutathione (GSH) content, and expression of P-glycoprotein (P-gp). When compared to parental cells, ρ0 cells resulted much less sensitive to apoptosis. MMP was well maintained in ρ0 cells, and remained unchanged after adding apoptogenic agents, and did not change after treatment with molecules able to depolarize mitochondria such as valinomycin. After adding STS, the production of reactive oxygen species was similar in both cell types, but ρ0 cells maintained higher levels of GSH. In ρ0 cells, P-gp was strongly over-expressed both at mRNA and protein level, and its functionality was higher. The resistance to apoptosis of ρ0 cells could be not only due to an increased scavenger capacity of GSH, but also due to a selection of multidrug resistant cells that hyperexpress P-gp.
AB - Cells lacking mitochondrial genome (defined as ρ0) are useful models in studies on cancer, aging, mitochondrial diseases and apoptosis, but several of their functional aspects have been poorly characterized. Using different clones of ρ0 cells derived from the human osteosarcoma line 143B, we have tested the effects of different apoptogenic molecules such as staurosporine (STS), doxorubicin, daunomycin and quercetin, and have analyzed apoptosis, mitochondrial membrane potential (MMP), levels of oxygen free radicals, reduced glutathione (GSH) content, and expression of P-glycoprotein (P-gp). When compared to parental cells, ρ0 cells resulted much less sensitive to apoptosis. MMP was well maintained in ρ0 cells, and remained unchanged after adding apoptogenic agents, and did not change after treatment with molecules able to depolarize mitochondria such as valinomycin. After adding STS, the production of reactive oxygen species was similar in both cell types, but ρ0 cells maintained higher levels of GSH. In ρ0 cells, P-gp was strongly over-expressed both at mRNA and protein level, and its functionality was higher. The resistance to apoptosis of ρ0 cells could be not only due to an increased scavenger capacity of GSH, but also due to a selection of multidrug resistant cells that hyperexpress P-gp.
KW - Apoptosis
KW - Mitochondrial DNA
KW - Mitochondrial membrane potential
KW - P-glycoprotein
KW - Reduced glutathione
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U2 - 10.1002/cyto.a.20544
DO - 10.1002/cyto.a.20544
M3 - Article
C2 - 18302187
AN - SCOPUS:44949185645
VL - 73
SP - 528
EP - 537
JO - Cytometry. Part A : the journal of the International Society for Analytical Cytology
JF - Cytometry. Part A : the journal of the International Society for Analytical Cytology
SN - 1552-4922
IS - 6
ER -