230 PALMITIC ACID TRIGGERS CELL DEATH IN PC12 CELLS THROUGH THE ACTIVATION OF MITOCHONDRIAL PROAPOPTOTIC GENES

The present study uses PC12 cells to investigate the mechanism by which pathological concentrations of saturated free fatty acids (FFAs) trigger cell death. Fatty acid-induced apoptotic cell death has been proposed to play a role in the neuronal loss observed following traumatic injury in the CNS and PNS. To further study this observation, we performed a series of c-DNA array experiments using mRNA of PC12 cells exposed to palmitic acid complexed with bovine serum albumin (BSA) (2:1 ration). Our data show that palmitic acid changes the levels of expression of several mRNAs of proteins that have been associated with apoptosis such as BNIP3 and Bax. Quantitative real-time RT-PCR (QRTPCR) experiments revealed an up-regulation of the proapoptotic mRNA BNIP3 that reached a maximum of 4-fold induction and Bax that reached a maximum of 3.5 induction during the course of the exposure of PC12 cells to palmitic acid. Western blots results also show an induction in BNIP3 and Bax protein. Additional activation of BNIP3/Bax can induce cell death by heterodimerization with antiapoptotic Bcl-2/Bcl-xl or by opening of the permeability transition pore resulting in mitochondrial dysfunction. Our results suggest that saturated FFAs induced cell death through the activation of proapoptotic mitochondrial genes like BNIP3 and Bax.