Differential effects of PCBs on the induction of apoptosis machinery and PKCalpha translocation in rat renal tubular cell cultures.
We have demonstrated previously [Pérez-Reyes, P.L., Sánchez-Alonso, J.A., López-Aparicio, P., Recio, M.N., Pérez-Albarsanz, M.A., 2001. Different molecular capacity in the induction of apoptosis by polychlorinated biphenyl congeners in rat renal tubular cell cultures. Biosci. Rep. 6, 765-778] that the polychlorinated biphenyls (PCBs) cause loss of cell viability and accelerate apoptosis in cell kidney cultures. Further investigations are necessary to elucidate the mechanism of apoptosis induction. In this way, we have analyzed in the present work the effects of PCBs on protein kinase C (PKC, a protein family intimately involved in the regulation of cell survival) and the expression of two proapoptotic (caspase-3 and Bax) and one antiapoptotic (Bcl-2) proteins. Aroclor 1248 (a commercial PCB mixture with 48% chlorine by weight), PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl, a di-ortho-substituted nonplanar congener) and PCB 77 (3,3',4,4'-tetrachlorobiphenyl, a non-ortho-substituted planar congener), significantly increased PKCalpha activity compared to control cells in the cytosolic and particulate cell fractions, and increased the PKCalpha protein content in the particulate fraction. The nonplanar PCB 153 showed stronger effects than the coplanar congener PCB 77. In addition, Aroclor 1248 decreased both, procaspase-3 levels and the Bcl-2/Bax protein ratio. These findings indicate that PCBs, particularly nonplanar congeners, can induce apoptosis in primary renal tubular cells through the PKCalpha, caspase-3 and Bcl-2/Bax pathway.
Santiago
Mercedes Fernández
MF
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
Pérez-Reyes
Pedro L
PL
López-Aparicio
Pilar
P
Recio
María N
MN
Pérez-Albarsanz
Miguel A
MA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001140:Aroclors / Q000633:toxicity; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002458:Cell Fractionation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D007684:Kidney Tubules / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051571:Protein Kinase C-alpha / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D001140:Aroclors; C494828:Bax protein, rat; D004785:Environmental Pollutants; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C028617:aroclor 1248; D011078:Polychlorinated Biphenyls; D051571:Protein Kinase C-alpha; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C028451:3,4,3',4'-tetrachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl