Over-expression Of HPO205 Promotes SMMC7721 Hepatoma Cell Survival In A Sulfhydryl Oxidase-dependent Manner

HPO205, cloned from human fetal liver cDNA library, is an FAD-dependent sulfhydryl oxidase and a member of Ervlp/Alrp protein family. The highly conserved special CXXC motif in the carboxyl terminus of this family is essential for their sulfhydral oxidase activity. Previous studies demonstrate that HPO, as a human homologe of Ervlp, plays very important roles in regulation of hepatocyte proliferation. HPO205 is a new isoform of HPO, whose N-terminal contains another 80 amino acids. The function of HPO205 is still obscure. Here we established a Myc-tagged HPO205 stable high expressed single cell clone as well as its mutation of CXXC. We found that HPO205 is localized at mitochondria as a form of homodimer. Its over-expression dose not promote the proliferation of SMMC7721 hepatoma cell, but inhibits cell death induced byγ-ray radiation and H₂O₂ When cells were treated with 20Gry ⁶⁰Co γ-ray radiation or 100μM H₂O₂, there were much less apoptosis in HPO205 over-expressing cells compared with the contro cells. We also found that HPO205 could decrease the level of ROS, stabilize the potential of mitochondrial membrane and enhance the productivity of ATP. But this is not the case in mutated HPO205 over-espressing cells. These results suggest that HPO205 promotes cell survival by strengthening the function of mitochondrial in a sulfhydryl oxidase-dependent manner.What's more, previous work prompts us that HPO205 may be involved in spermatogenesis, so a testis specific express vector has been constructed and a transgenic mice model will be established.