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. Fulceri et al., 1995, Biochem. J. 307, 391-397), conflicting ideas as to histone II-A's mechanism of activation have been described (J. St.-Denis et al., 1995, Biochem. J. 310, 221-224 and J. Blair and A. Burchell, 1988, Biochim. Biophys. Acta 964, 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 by N-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.
Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202, USA.
B A
BA
Pederson
J D
JD
Foster
R C
RC
Nordlie
D000408:Alamethicin / Q000494:pharmacology; D000818:Animals; D002384:Catalysis; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D006657:Histones / Q000494:pharmacology*; D043564:Inorganic Pyrophosphatase; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D017830:Octoxynol / Q000494:pharmacology; D010848:Picolinic Acids / Q000494:pharmacology; D011755:Pyrophosphatases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004983:Ethanolamines; D006657:Histones; D010848:Picolinic Acids; D000408:Alamethicin; C020161:N-bromoacetylethanolamine phosphate; C008363:3-mercaptopicolinic acid; D017830:Octoxynol; D005952:Glucose-6-Phosphatase; D011755:Pyrophosphatases; D043564:Inorganic Pyrophosphatase