scholarly journals A distinctive histidine residue is essential for in vivo glycation-inactivation of human CD59 transgenically expressed in mice erythrocytes: Implications for human diabetes complications

2017 ◽  
Vol 92 (11) ◽  
pp. 1198-1203 ◽  
Author(s):  
Rupam Sahoo ◽  
Pamela Ghosh ◽  
Michael Chorev ◽  
Jose A. Halperin
Keyword(s):  
Diabetes Complications ◽  
Histidine Residue ◽  
Human Diabetes ◽  
Human Cd59

Biogenic integrated ZnO/Ag nanocomposite: Surface analysis and in vivo practices for the management of type 1 diabetes complications

2020 ◽  
Vol 189 ◽  
pp. 110878 ◽  
Author(s):  
Shima Rahim Pouran ◽  
Abolfazl Bayrami ◽  
Farid Mohammadi Arvanag ◽  
Aziz Habibi-Yangjeh ◽  
Reza Darvishi Cheshmeh Soltani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Surface Analysis ◽  
Diabetes Complications

Proliferative and Cytokine Responses in CTLA4-Ig-Treated Diabetic NOD Mice Transplanted with Microencapsulated Neonatal Porcine ICCs

2002 ◽  
Vol 11 (7) ◽  
pp. 695-705 ◽  
Author(s):  
Susan A. Safley ◽  
Judith A. Kapp ◽  
Collin J. Weber
Keyword(s):  
Graft Function ◽  
Nod Mice ◽  
Spleen Cells ◽  
High Background ◽  
Effector Cells ◽  
Xenograft Rejection ◽  
Porcine Islet ◽  
Human Diabetes

Our goal is to develop effective islet xenografts for treating human diabetes. We have studied microencapsulated neonatal porcine islet cell clusters (ICCs) transplanted intraperitoneally in spontaneously diabetic NOD mice, where they function to maintain normoglycemia in the autoimmune host. Nonencapsulated neonatal porcine ICCs functioned for 4.5 ± 0.5 days before being rejected; encapsulation prolonged graft function to 17 ± 2 days. CTLA4-Ig treatment did not enhance the survival of nonencapsulated ICCs. However, CTLA4-Ig treatment significantly extended the function of encapsulated ICCs to 73 ± 5 days. Histological analyses demonstrated a profuse pericapsular cellular reaction associated with rejection of encapsulated islet xenografts in untreated mice, while this reaction was significantly reduced in CTLA4-Ig-treated mice. To study mechanisms of xenograft rejection in this model, we analyzed proliferative responses to neonatal porcine ICCs and cytokines present in the peritoneal cavities of transplanted mice. Spleen cells from both CTLA4-Ig-treated and untreated rejecting NODs exhibited vigorous proliferation in the absence of antigenic stimulation, suggesting prior activation in vivo, while splenocytes from CTLA4-Ig-treated NODs with functioning grafts had low proliferative levels, equal to controls. Islet-specific proliferation was not detected in islet-rejecting mice, perhaps due to their high background levels. With the exception of elevated IL-6 levels, empty capsules did not provoke a significant peritoneal cytokine response compared with sham surgery or untransplanted control mice. However, IL-5, IL-12, TGF-β, and IL-1β were significantly elevated in NODs receiving encapsulated neonatal porcine ICCs compared with untransplanted controls. There were no significant differences between peritoneal cytokine concentrations in CTLA4-Ig-treated mice with long-term functioning grafts compared to mice that rejected grafts at earlier time points. We conclude that the combination of donor islet microencapsulation and brief treatment of the recipient with co-stimulatory blockade delays sensitization of the host, possibly by altering mechanism(s) for recruitment and/or activation of host effector cells.

Regulation of SulA cleavage by Lon protease by the C-terminal amino acid of SulA, histidine

2001 ◽  
Vol 358 (2) ◽  
pp. 473-480 ◽  
Author(s):  
Yoshiyuki ISHII ◽  
Fumio AMANO
Keyword(s):  
Amino Acid ◽  
Protein A ◽  
Lon Protease ◽  
Histidine Residue ◽  
High Accumulation ◽  
C Terminus ◽  
A Cell ◽  
Cell Division Inhibitor

SulA protein, a cell division inhibitor in Escherichia coli, is degraded by Lon protease. The C-terminal eight residues of SulA have been shown to be recognized by Lon; however, it remains to be elucidated which amino acid in the C-terminus of SulA is critical for the recognition of SulA by Lon. To clarify this point, we constructed mutants of SulA with changes in the C-terminal residues, and examined the accumulation and stability of the resulting mutant SulA proteins in vivo. Substitution of the extreme C-terminal histidine residue with another amino acid led to marked accumulation and high stability of SulA in lon+ cells. A SulA mutant in which the C-terminal eight residues were deleted (SulAC161) showed high accumulation and stability, but the addition of histidine to the C-terminus of SulAC161 (SulAC161+H) made it labile. Similarly, SulAC161+H fused to maltose-binding protein (MBP–SulAC161+H) formed a tight complex with and was degraded rapidly by Lon in vitro. Histidine competitively inhibited the degradation of MBP–SulA by Lon, while other amino acids did not. These results suggest that the histidine residue at the extreme C-terminus of SulA is recognized specifically by Lon, leading to a high-affinity interaction between SulA and Lon.

scholarly journals Characterization in vitro and in vivo of the pig analogue of human CD59 using new monoclonal antibodies

Immunology ◽  
1998 ◽  
Vol 95 (3) ◽  
pp. 450-459 ◽  
Author(s):  
HANNA ◽  
WILLIAMS ◽  
VAN DEN BERG ◽  
MORGAN
Keyword(s):  
Monoclonal Antibodies ◽  
Human Cd59

Protection of erythrocytes from human complement–mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2131-2137 ◽  
Author(s):  
Anita Hill ◽  
Simon H. Ridley ◽  
Dirk Esser ◽  
Rodney G. Oldroyd ◽  
Matthew J. Cullen ◽  
...  
Keyword(s):  
Human Complement ◽  
New Approach ◽  
Esophageal Spasm ◽  
Severe Fatigue ◽  
Acute Exacerbations ◽  
Chronic Hemolysis ◽  
Cd1 Mice ◽  
Human Cd59

Paroxysmal nocturnal hemoglobinuria (PNH) results from the expansion of a hematopoietic clone that is deficient in glycosylphosphatidylinositol-anchored molecules. PNH is characterized by chronic hemolysis with acute exacerbations due to the uncontrolled activity of complement on PNH cells, which lack the inhibitor of homologous complement, CD59. Symptoms include severe fatigue, hemoglobinuria, esophageal spasm, erectile dysfunction, and thrombosis. We report the use of a novel synthetically modified recombinant human CD59, rhCD59-P, a soluble protein that attaches to cell membranes. In vitro treatment of PNH erythrocytes with rhCD59-P resulted in levels of CD59 equivalent to normal erythrocytes and effectively protected erythrocytes from complement-mediated hemolysis. The administration of rhCD59-P to CD1 mice resulted in levels of CD59 on erythrocytes, which protected them from complement-mediated lysis. Thus, rhCD59-P corrects the CD59 deficiency in vitro and can bind to erythrocytes in an in vivo murine model, protecting the cells from the activity of human complement, and represents a potential therapeutic strategy in PNH.

scholarly journals Functional implications of ribosomal protein L2 in protein biosynthesis as shown by in vivo replacement studies

1998 ◽  
Vol 331 (2) ◽  
pp. 423-430 ◽  
Author(s):  
Monika ÜHLEIN ◽  
Wolfgang WEGLÖHNER ◽  
Henning URLAUB ◽  
Brigitte WITTMANN-LIEBOLD
Keyword(s):  
Ribosomal Proteins ◽  
Protein Biosynthesis ◽  
Complex Structure ◽  
Peptide Bond ◽  
Histidine Residue ◽  
Peptide Bond Formation ◽  
Homologous Proteins ◽  
Translational Activity ◽  
Translational Apparatus

The translational apparatus is a highly complex structure containing three to four RNA molecules and more than 50 different proteins. In recent years considerable evidence has accumulated to indicate that the RNA participates intensively in the catalysis of peptide-bond formation, whereas a direct involvement of the ribosomal proteins has yet to be demonstrated. Here we report the functional and structural conservation of a peptidyltransferase centre protein in all three phylogenetic domains. In vivo replacement studies show that the Escherichia coli L2 protein can be replaced by its homologous proteins from human and archaebacterial ribosomes. These hybrid ribosomes are active in protein biosynthesis, as proven by polysome analysis and poly(U)-dependent polyphenylalanine synthesis. Furthermore, we demonstrate that a specific, highly conserved, histidine residue in the C-terminal region of L2 is essential for the function of the translational apparatus. Replacement of this histidine residue in the human and archaebacterial proteins by glycine, arginine or alanine had no effect on ribosome assembly, but strongly reduced the translational activity of ribosomes containing these mutants.

scholarly journals Functional and antigenic similarities between a 94-kD protein of Schistosoma mansoni (SCIP-1) and human CD59.

1994 ◽  
Vol 179 (5) ◽  
pp. 1625-1636 ◽  
Author(s):  
M Parizade ◽  
R Arnon ◽  
P J Lachmann ◽  
Z Fishelson
Keyword(s):  
Schistosoma Mansoni ◽  
Membrane Attack Complex ◽  
Protein S ◽  
Immunogold Electron Microscopy ◽  
Mammalian Host ◽  
Inhibitory Protein ◽  
Host Immune Responses ◽  
The Third World ◽  
Human Cd59

Schistosomiasis is a parasitic disease affecting approximately 200 million people, primarily in the third world. Schistosoma mansoni, one of the causative agents of this disease, parasitize the human mesenteric and portal blood systems while successfully evading host immune responses. During parasite penetration into the mammalian host and shortly afterwards, the larvae rapidly convert from being sensitive to being resistant to C-mediated killing. Treatment of the C-resistant parasitic forms with trypsin renders the parasite susceptible to C attack, thus indicating the presence of C inhibitory protein(s) on the parasite surface. We describe here an intrinsic schistosome C inhibitory protein (SCIP-1) that exhibits antigenic and functional similarities with the human C-inhibitor CD59. Like CD59, SCIP-1 is capable of inhibiting formation of the C membrane attack complex (MAC), probably by binding to C8 and C9 of the C terminal pathway. In addition, SCIP-1 is apparently also membrane-anchored via glycosyl phosphatidylinositol as it can be specifically released with phosphatidylinositol-specific phospholipase C. Soluble SCIP-1, partially purified from Nonidet P-40 extracts of schistosome tegument is capable of inhibiting hemolysis of sensitized sheep erythrocytes and of rabbit erythrocytes by human C. Anti-human CD59 antibodies block this activity of SCIP-1 and in addition, upon binding to intact parasites, render them vulnerable to killing by human and guinea pig C. SCIP-1 is located on the surface of C-resistant forms of the parasite, i.e., 24-h cultured mechanical schistosomula and in vivo-derived adult worms as revealed by immunofluorescence and immunogold electron microscopy studies. These results identify one of the mechanisms schistosomes use to escape immune attack.

Characterization of the transition-metal-binding properties of hepcidin

2010 ◽  
Vol 427 (2) ◽  
pp. 289-296 ◽  
Author(s):  
Chris Tselepis ◽  
Samuel J. Ford ◽  
Andrew T. McKie ◽  
Wolfgang Vogel ◽  
Heinz Zoller ◽  
...  
Keyword(s):  
Metal Ions ◽  
Metal Binding ◽  
Biological Effects ◽  
Point Mutations ◽  
Peptide Hormone ◽  
Histidine Residue ◽  
Ferrous Ions ◽  
Protein Levels ◽  
Bivalent Metal Ions

Accumulating evidence suggests that hepcidin, a 25-residue peptide hormone, is the master regulator of iron metabolism. Further evidence suggests that the five N-terminal amino acids are crucial for mediating its biological function. With a histidine residue at position 3, this region also has the potential to bind bivalent metal ions. To characterize this hepcidin–metal interaction in detail, the present study utilizes electrospray MS to measure the binding of a range of metal ions to wild-type and mutant human and murine hepcidins. In addition, the biological effects of these point mutations were tested on Caco-2 and HEK-293T human cell lines and in mice. Our results show that hepcidin-25 can form complexes with copper, nickel and zinc; however, we failed to detect any hepcidin-25 binding to either ferric or ferrous ions. The greatest affinity observed was between hepcidin-25 and copper with a dissociation constant ≪1 μM. Substituting the histidine residue at position 3 in human hepcidin-25 and comparably the asparagine residue at position 3 in murine hepcidin-25 with an alanine residue markedly diminished the affinity for copper. The amino acid substitutions also decreased the biological activity of hepcidin-25; namely repression of ferroportin protein levels and hypoferraemia. In summary, the high affinity of hepcidin for copper suggests that hepcidin could bind copper in vivo and this may be of biological relevance.

Sign in / Sign up

Export Citation Format

Share Document