Effects of Hypoxia on the Ubiquitin-proteasome System in Primary Cortical Neuronal Cell Cultures / 체질인류학회지

ABSTRACT

The ubiquitin-proteasome system is crucial in maintaining cellular growth and metabolism. Dysfunction of this system may contribute to neurodegenerative diseases, such as Parkinson's disease. But its effects on primary neurons are largely unknown. In the present study, we investigated the effects of proteasome inhibitor and hypoxia on primary neuronal cultures to determine whether proteasomal malfunction induces neuronal death. Neuronal apoptosis increased in primary cultured cortical neurons with treatment of proteasomal inhibitor in normoxic condition and in the presence or absence of proteasomal inhibitor in hypoxic condition. Also expression of PARP and activated caspase 3 increased. NF-kappaB, a key transcription factor in this system expression increased in hypoxic condition and proteasomal inhibition. Interestingly, hypoxic condition induced an expression and accumulation of alpha-synuclein in neuron, one of components of Lewy body in Parkinson's disease. Our findings determine that hypoxic condition may affect the ubiquitin-proteasome system. Furthermore, it suggests that hypoxic condition and proteasomal inhibitors are involved, at least in parts, in neurodegeneration of mouse model for Parkinson's disease.