Histone II-A Activates the Glucose-6-Phosphatase System without Microsomal Membrane Permeabilization

Many agents have been used to release the latent portion of the activities catalyzed by the glucose-6-phosphatase (Glc-6-Pase) system. Detergents, which disrupt the microsomal membrane concomitantly with Glc-6-Pase activation, have been the most widely used of these agents. The treatment of microsomes with alamethicin or histone II-A has also been reported to activate the Glc-6-Pase system to the same extent as detergent treatment. While alamethicin reportedly permeabilizes the microsomal membrane (R. Fulceriet al.,1995,Biochem. J.307, 391–397), conflicting ideas as to histone II-A's mechanism of activation have been described (J. St.-Deniset al.,1995,Biochem. J.310, 221–224 and J. Blair and A. Burchell, 1988,Biochim. Biophys. Acta964, 161–167). We further investigated whether activation of the Glc-6-Pase system by histone II-A is due to permeabilization of the microsomal membrane. We treated rat liver microsomes with Triton X-100, alamethicin, or histone II-A and found them to be equally effective in maximally activating the Glc-6-Pase system. We also examined the modifying effects of alamethicin and histone II-A on the sensitivity of Glc-6-Pase activities to inhibition byN-bromoacetylethanolamine phosphate (BAEP) and 3-mercaptopicolinate (3-MP), both thiol-directed reagents. Alamethicin, but not histone II-A, abolished the inhibitory effects of BAEP and 3-MP on activities of the Glc-6-Pase system. Our studies support previous reports of Glc-6-Pase activation by alamethicin via permeabilization of microsomal membranes and histone II-A activation without microsomal membrane permeabilization.