Molecular mechanisms involved in PTH-induced apoptosis in Caco-2 intestinal cells

CALVO NATALIA; BOLAND, RICARDO; RUSSO DE BOLAND ANA; GENTILI CLAUDIA

Quebec, Canadá

Congreso; Annual Meeting ASBMR (American Society for Bone and Mineral Research); 2008

ASBMR (American Society for Bone and Mineral Research)

Apoptosis, a form of programmed cell death, is a process fundamental to normal growth and development, immune response, tissue remodeling after injury or insult, and plays a critical role in maintaining homeostasis of the intestinal epithelium. Recently, it has become apparent that signaling by the PTH receptor can either promote or suppress apoptosis depending on the cellular context. In this study we show that stimulation of human colonic Caco-2 cells with PTH (10-8 M) results in the dephosphorylation and translocation of pro-apoptotic protein Bad from the cytosol to mitochondria and release of cytochrome c and Smac/Diablo. The hormone also triggers mitochondria cellular distribution to the perinuclear region, diminishes the number of viable cells, increases the enzymatic activity of caspase-3, that is also evidenced from the appearance of its cleaved fragments in western blot experiments, and degradation of its substrate PARP. Moreover, we found that the hormone induces disruption of actin filaments with changes of cellular shape, alteration of cell-to-cell junctions, externalization of membrane phosphatidylserine and also chromatin condensation and DNA fragmentation of the nucleus. Taken together, the present study suggests that the mitochondrial pathway  may account  for PTH promotion of apoptosis in Caco-2 intestinal cells.