Transferrin and Ferritin Modulate the Activity of Brain Calcium-Calmodulin-Dependent Phosphodiesterase

M. G. Yefimova,^1,2 I. S. Shcherbakova,¹ and N. D. Shushakova¹

¹Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Morisa Toreza 44, St. Petersburg, 194223 Russia; fax: (7-812) 552-30-12; E-mail: snk@ief.spb.su

²To whom correspondence should be addressed.

Submitted July 17, 1996; revision submitted October 10, 1996.

The effect of the key iron homeostasis proteins transferrin and ferritin on the activity of partially purified brain calcium-calmodulin-dependent phosphodiesterase (CaM-PDE, EC 3.4.1.17) were studied. Transferrin and ferritin were found to be potent natural activators of CaM-PDE. The key factor determining the degree of activation by these proteins is their saturation with iron: apotransferrin activated CaM-PDE 6-7-fold; iron-poor brain ferritin and liver apoferritin (taken for comparison) activated the enzyme 4-5- and 2-fold, respectively. Diferric transferrin and iron-rich liver ferritin had no effects on the enzyme activity. Transferrin and ferritin (both in apo- and iron-saturated forms) did not change the activity of calmodulin--phosphodiesterase complex. The data suggest that apotransferrin and iron-poor transferrin are involved in the regulation of cyclic nucleotide content in nervous tissue.

KEY WORDS: transferrin, ferritin, phosphodiesterase, brain, iron.

---