Maturation Of Alpha Research Articles

Role of endoplasmic reticular calcium in oligosaccharide processing of alpha 1-antitrypsin.

Mobilization of Ca2+ from the endoplasmic reticulum (ER) suppresses translational initiation and inhibits post-translational processing and secretion of glycoproteins. This study explores the mechanism whereby ionomycin, a Ca2+ ionophore, and thapsigargin, an ER Ca(2+)-ATPase inhibitor, promote retention of alpha 1-antitrypsin (alpha 1-AT) bearing high mannose, endoglycosidase H (Endo H)-sensitive oligosaccharide side chains within the ER of HepG2 cells. Arrest occurred at the removal of mannose residues such that intermediates with Man7-9GlcNAc2 side chains accumulated with the Man8-9GlcNAc2 structures predominating. Maturation of alpha 1-AT bearing Man5-6GlcNAc2 side chains was unaffected. Inhibition of alpha 1-AT processing by ionomycin occurred independently of translational suppression. Forms of alpha 1-AT identical to those retained with ionomycin or thapsigargin were observed upon treatment with the alpha-1,2-mannosidase inhibitor 1-deoxymannojirimycin whereas castanospermine, an inhibitor of ER alpha-glucosidase I, produced different forms of the glycoprotein. Neither inhibitor impaired transport or secretion of alpha 1-AT. With brefeldin A, which causes redistribution of Golgi enzymes to the ER, alpha 1-AT was retained intracellularly but acquired resistance to Endo H. With ionomycin, thapsigargin, or 1-deoxymannojirimycin-treated cells, however, brefeldin A failed to promote further processing of the glycoprotein. Possible mechanisms for the suppression of alpha 1-AT processing at the alpha-1,2-mannosidase step by Ca(2+)-mobilizing agents are discussed. Excepting tunicamycin, traditional inhibitors of protein processing did not affect amino acid incorporation.

The Possible Role of Androgenic Hormones in Maturation of Alpha2‐Adrenergic Mechanisms in the Rat

Abstract In order to get better characterization of androgenic hormones on the functionality of the alpha(2)-adrenergic system and widen our previous studies, we investigated the effect of clonidine on the growth hormone (GH) secretion in male Wistar rats of various ages: 7-, 14- and 30-day old and adult, adult male castrated rats with and without testosterone treatment. Two different patterns of the GH response to clonidine have been observed in the control and testosterone-treated young animals: clonidine at the dose 15 mug/kg intraperitoneally had no effect on the GH secretion in 7- to 14-day old rat pups. In contrast, its effect appeared following the increase in the plasma testosterone concentration induced by pretreatment with testosterone (5 mg/kg subcutaneously for 4 days) in these animals. In 30-day old rats clonidine affected GH secretion and this influence was more pronounced in the testosterone-treated animals than in the controls. The decrease in the circulating testosterone levels caused by castration in adult male rats caused a decreased GH response to clonidine. Moreover, there was a tendency for the GH response to return in 4-week old animals. The effect of clonidine has been restored by testosterone replacement of castrates. Testosterone administration decreased basal plasma GH levels in the pups. However, it triggered the ultradian surges of GH secretion which were absent in the young animals. Clonidine had no effect on the corticosterone secretion in 7-day old animals. Testosterone treatment induced a response in the 7-day old rat and markedly potentiated its effect on the secretion of this hormone in 14- and 30-day old animals, respectively. Neither progesterone nor hydrocortisone influenced the GH-releasing effect of clonidine. Hydrocortisone markedly inhibited the basal- and clonidine-induced corticosterone secretion. The results of the present study indicate an important role of androgenic hormones in inducing and/or maintaining the effectiveness/sensitivity of the alpha(2)-adrenergic receptor system and suggest a possible role for the androgenic hormones in the maturation of alpha-adrenergic mechanisms in the rat.