THE ROLE OF INDUCIBLE TRANSCRIPTION FACTORS IN APOPTOTIC NERVE-CELL DEATH

Recent studies have shown that certain types of nerve cell death in the brain occur by an apoptotic mechanism. Researchers have demonstrated that moderate hypoxic-ischemic (HI) episodes and status epilepticus (SE) can cause DNA fragmentation as well as other morphological features of apoptosis in neurons destined to die, whereas more severe HI episodes lead to neuronal necrosis and infarction. Although somewhat controversial, some studies have demonstrated that protein synthesis inhibition prevents HI-and SE-induced nerve cell death in the brain, suggesting that apoptotic nerve cell death in the adult brain is de novo protein synthesis-dependent (i.e., programmed). The identity of the proteins involved in HI-and SE-induced apoptosis in the adult brain is unclear, although based upon studies in cell culture, a number of potential cell death and anti-apoptosis genes have been identified. In addition, a number of studies have demonstrated that inducible transcription factors (ITFs) are expressed for prolonged periods in neurons undergoing apoptotic death following HI and SE. These results suggest that prolonged expression of ITFs (in particular c-jun) may form part of the biological cascade that induces apoptosis in adult neurons. These various studies are critically discussed and in particular the role of inducible transcription factors in neuronal apoptosis is evaluated.