Effect Of P300 And P300-binding Properties On The Neuron Injury During Hypoxia

Hypoxia is a common injury factor in many clinical diseases and some specific environments such as high altitude, aviation and diving. Central nervous system (CNS) is extremely dependent on a constant oxygen supply. Any disturbance in this supply becomes life-threatening and may result in severe and irreversible loss of brain function. Exploring the mechanisms of neuron injury during hypoxia and looking for approaches to enhance CNS hypoxia tolerance are major topics in the field of neuroscience and high altitude medicine.Gene differential expression is not only the critical process for modulating cellular homeostasis, but also the basic response of living body to external stimuli. It becomes the essential purpose to explore the gene expression and regulation patterns induced by hypoxic stress in the CNS and understand their relations with neuron damage. Besides transcriptional factors, the transcriptional coactivators also play a most important role in the gene expression and regulation. Essentially, given the complexity of their protein binding property, coactivators serves as signal integrators to connect the stimulus and gene expression directly and participate to make a decision for gene differential expression. With the essentiality of the gene regulation network in the functional genomic reseach, the transcriptional coactivators have been a focus recent years.The transcriptional coactivator p300 interacts with a large group of transcription factors that participate in the gene expression regulating numerous biological process including cell differentiation, proliferation, apoptosis, oxygen homeostasis and growth control.It is a necessary modulor of hypoxic gene expression because of its definite role in the transcriptional activation of HIF-1, NF-kB, AP-1 and c-Jun, p53and so on. Nevertheness, p300 is a critical protein to prevent neurons from degeneration. So, we hypothesize that p300 may be a necessary regulator participated in the hypoxic adaptation and injury process.