Elevated levels of Ca(II) modulate the activity and inhibition of serine proteases: Implication in the mechanism of apoptosis

Elevated levels of intracellular Ca(II) are a prominent feature of apoptosi s, a natural form of cell death involved in many physiological and patholog ical processes. Serine proteases play crucial roles in apoptosis and have b een implicated in the genomic DNA degradation and the massive protein degra dation that occur during apoptosis. In this study, the effects of the eleva ted level of Ca(II) on the activity and inhibition of serine proteases were examined by spectrophotometric methods. The effects of the elevated levels of Ca(II), Mg(II), K(I), and Na(I) on the activity and inactivation of thr ee representative members of serine proteases were determined. The level of serine protease activity in CEM-C7-14 leukemic cells was also evaluated in the presence and absence of dexamethasone-induced apoptosis, and also in t he presence of A23187, a Ca(II)-ionophore. Among the four metal-ions studie d, only Ca(II) was found to significantly enhance the activity of mammalian serine proteases. Ca(II) was also found to significantly protect the enzym es from inhibition. while the other three metal-ions showed no significant effect on the inactivation of the enzymes. Compared to the control sampler the enzymic activity was found to be higher during apoptosis, and in the pr esence of the Ca(II)-ionophore. Results of this study indicate that Ca(II) can significantly enhance the catalytic efficiency of serine proteases duri ng apoptosis. Copyright (C) 2000 John Wiley & Sons, Ltd.