Activity And Mechanism Of Hypoxia-inducible Factor 1 Related Peptide

Hypoxia may be implicated in the pathogenesis of many disease including stroke and heart attack. Adequate oxygen delivery is essential for neural tissue to generate its normal functions. Hypoxia-inducible factor 1 (HIF-1) protein is a nuclear protein with the function of transcriptional regulation and is the direct sensor of hypoxia. HIF-1 activity could be induced under hypoxia or in the presence of Co²+ or Fe²+ chelating agent. HIF-1 plays a important role by regulating its downstream genes involved erythropoietin (EPO), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), inducible nitric oxide synthase (iNOS) and heme oxygenase (HO).Our previous study found that suppress of HIF-1 was correlated with PC 12 cell injury, and HIF-1 α antisense oligonucleotide could inhibit SOD activity, increase levels of LDH and MDA. The sequences screened from 12-mer phage library were compared with HIF1 a sequence in GenBank. The central sequence (5 amino acids) of HIF-1 a relative peptide was determined. The physical and chemical characterization of candidate peptides (10-20 amino acids) was tested by Antheprot software. Peptide BW8 (GLAP*YIGPHH, P*: oxyproline) was found to have protective role in PC 12 cells, myocardial cells and mesangial cells. 1. Protection of BW8 against cell injury.Cultured PC 12 cells, cardiac muscle cells and rat mesangial cells were treated by CoCl₂, KCl and H₂O₂ respectively, the protective effects...