アルミニウムイオンのカルシニューリン活性に対する影響

抄録

Aluminum (Al) is the third-most abundant metal and is widely distributed in our environment. It is stable as a trivalent ion and is not an essential trace element for humans. Aluminum compounds are industrially used as pharmaceuticals, food additives, cosmetics, and other household products. For pharmaceutical applications, aluminum salts are used as adjuvants to prepare vaccines and sucralfate, a complex of aluminum hydroxide and sulfated sucrose with an antiulcer property. However, Al is reported to be associated with the development of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.
Calcineurin (CN)，a target enzyme for immunosuppressive drugs such as tacrolimus (FK506) and cyclosporine A, is a calcium ion (Ca ^{2 +} )/calmodulin (CaM)-dependent protein serine/threonine phosphatase. We previously confirmed that trivalent lanthanum (La [III])，trivalent scandium (Sc [III])，trivalent yttrium (Y [III])，and trivalent chromium (Cr [III]) can inhibit the phosphatase activity of recombinant human CN (rhCN) from Escherichia coli. Kinetic analysis revealed that the inhibition was a mixed-type inhibition for La (III) and a non-competitive inhibition for Cr (III). In the present study, we examined the effect of rhCN on phosphatase activity using trivalent aluminum (Al [III]). We observed that the Al (III) inhibition of rhCN activity was a mixed-type inhibition using a double-reciprocal Lineweaver–Burk plot.