Apoptosis in salmonid cell lines: the importance of apoptotic volume decrease, chloride fluxes and potassium fluxes in staurosporine-induced cell death

57) KRUMSCHNABEL, G., C. MANZL, P. J. SCHWARZBAUM

Glasgow, Escocia

Congreso; Meeting of the Society for Experimental Biology; 2007

Society for experimental biology

In numerous mammalian cell models apoptosis is associated with cell shrinkage. Inhibition of this apoptotic volume decrease by blockers of swelling-activated ion transporters has repeatedly found to be cytoprotective, suggesting that cell shrinkage is an important early event in this mode of cell death. In hepatoma and gill cells from rainbow trout staurosporine induced apoptosis, as assessed by activation of effector caspases, nuclear condensation, and a decrease of mitochondrial membrane potential (MMP), and these changes were accompanied by cell shrinkage,. The Cl- transport inhibitor DIDS and the K+ channel inhibitor quinidine both prevented apoptotic volume decrease, but only DIDS also inhibited apoptosis. Other inhibitors of Cl- fluxes such as SITS and NPPB did not prevent cell shrinkage, but still prevented caspase activation. Furthermore, although cyclosporine A, a blocker of the mitochondrial permeability transition pore (PTP), also inhibited the decrease of MMP, it did not prevent activation of caspases. Taken together, these results indicate that the protective effect of DIDS is not due to inhibition of cell shrinkage, but due to the blockage of Cl- fluxes activated upon staurosporine-exposure. In addition, it appears that not the inhibition of PTP opening, but possibly inhibition of mitochondrial outer membrane permeabilization is critical for the protective effect of DIDS.