Study Of The Relation Between The Expression Of β1,4-galactosyltransferase V And The Malignancy Of Human Astrocytoma

Astrocytoma is one of the most common malignant tumors in human central nervous system. Until now, the pathogenesis of astrocytoma has not been elucidated clearly. The researches on the changes and significance of β1,4-GalT V (GalT V) in malignancy of human astrocytoma will be helpful to make a prognosis of astrocytoma.In previous study, we have shown that GalT V functions as a positive growth regulator in glioma. Here we reported that down-regulation the expression of GalT V in SHG44 cells by transfection with antisense cDNA specifically up-regulated the expression of cell surface integrin β1 without the change of its mRNA, and with integrin β1 125 kD mature form increased and 105 KD precursor form decreased. It is well known that the N-glycans of integrins modulate the location and functions of integrins. The SHG44 cells transfected with antisense cDNA of GalT V demonstrated decreased Golgi localization of integrin β1, strengthened the interaction between integrin α5 and β1 subunit, and enhanced the adhesion ability to fibronectin and the level of focal adhesion kinase (FAK) phosphorylation. Our results suggested that the down-regulation expression of GalT V could promote the expression of cell surface integrin β1 and subsequently inhibit glioma malignant phenotype.Previous study showed that increased GalT V transcript which appeared in the process of astrocytoma progress with the highest level in grade IV. We found that the sequence of GalT V promoter between -200 and +120 were very important for GalT V transcription in SHG44 cells. More interestingly, this sequense showed specifically higher activity in SHG44 cells than in other cells. We found dose dependence up-regulation of the -200 ～ +120 GalT V promoter-Luc constructs activity by transfactor E1AF, which specifically high expression in SHG44 cells.Pyrrolo-quinoline quinine (PQQ), which has a molecular weight of 330, is purified from methanol-utilizing bacteria. Its crystal structure and chemical synthesis have been discovered. In recent years PQQ is also found in eucaryotes. Subsequent studies identified that PQQ is cofactor of many important enzymes in the bacteria and could affect function of electron transport chain and level of free radical in humanbody. Animal experiment indicated decelerated growth, decreased fertility and defects in immune function have occurred with PQQ-deficient mice. So PQQ is thought to role as an essential vitamin and helpful nutrient in vivo. Our experiment suggested that PQQ could treat lead poisoning and alcoholic fatty liver obviously.