Metal Ions Regulates Aggregation Of Glucagon

Recent studies show that many neuropathies such as Alzheimer's disease is associated with the aggregation in vivo of amyloid-like protein. The aggregation progress is not only dependent on the sequences of amino acids, but also closely related to the environmental factors such as metal ions, pH, temperature and so on. In this work, we not only observed the glucagon fibrillation with Fe(â…¢) , Cu(â…¡) and Zn(â…¡) , but also used Micro-FTIR to research into the secondary-structure of those fibers with Fe(â…¢) and Cu(â…¡) , we take the experiments in which the fibrillation was affected by metal ions coupled with temperature effects, in order to know more about mechanism of this aggregation, we carried out the "seeding experiments". The attained results reveal that: when added with Fe(â…¢) , the lag time of glucagon fibrillation was delayed, and morphology and secondary-structure of glucagon was changed greatly; when added with Cu(â…¡), the speed of this fibrillation was accelerated, and the morphology was not the same, but secondary-structure of this was unchanged; and another situation is added with Zn(â…¡), but there is only the result of clear distribution of the kinds of fibers, and it would be no change with the varied concentrations of Zn(â…¡) ; however, the effect will sharpen dramatically if concentration of Fe(â…¢) and Cu(â…¡) increases; and when metal ions effects coupled with temperature, glucagon with Fe(â…¢) may do good to formation of thinner fiber similar to TA fiber, and it has an hardly seen type of fiber in the solution with Cu(â…¡) , and when added with Zn(â…¡), there is no such evidently distribution of kinds of fiber in the solution. Thus, temperature will disturb the effects of metal ions, in the meanwhile, the "seeding experiments" will also do good to our further study of fibrillation of amyloid polypeptides.