scholarly journals Role of hemichrome binding to erythrocyte membrane in the generation of band-3 alterations in beta-thalassemia intermedia erythrocytes

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 2014-2020 ◽  
Author(s):  
F Mannu ◽  
P Arese ◽  
MD Cappellini ◽  
G Fiorelli ◽  
M Cappadoro ◽  
...  

Nine splenectomized, hematologically well-compensated beta-thalassemia intermedia patients randomly chosen from a pool of 60 similar patients were studied. Membrane proteins solubilized with nondenaturing detergent C12E8 were gel filtered on Sepharose CL-6B (Pharmacia Fine Chemicals, Uppsala, Sweden). Fractions containing higher than 4,000-kD molecular-weight aggregates were isolated and analyzed. Four patients had remarkably increased amounts of membrane-bound hemichromes and Igs. In those patients, band 3 underwent oxidative modifications such as aggregation and a decrease in sulfhydryl groups. The other five patients had low amounts of membrane-bound hemichromes and less modifications of band 3. The same band-3 modifications could be reproduced by challenging normal membranes with artificially generated hemichromes or with hemolysates prepared from thalassemic erythrocytes of the high-hemichrome group. Addition of reduced glutathione to the challenged membranes did not hinder hemichrome binding, but prevented oxidative modifications of band 3 and Ig binding to high-molecular- weight band-3 aggregates. Hemichrome binding to band 3, hemichrome- mediated oxidation of band-3 cytoplasmic domains, generation of high- molecular-weight band-3 aggregates, and enhanced opsonization by anti- band-3 antibodies is a possible sequence of events leading to phagocytic removal of erythrocytes in thalassemia.

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1068
Author(s):  
A. Mahesar ◽  
M. Mazari

2000 ◽  
Vol 275 (33) ◽  
pp. 25139-25145 ◽  
Author(s):  
David H. Ho ◽  
Karen Badellino ◽  
Frank A. Baglia ◽  
Mao-Fu Sun ◽  
Ming-Ming Zhao ◽  
...  

Materials ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 1077
Author(s):  
Romisuhani Ahmad ◽  
Mohd Mustafa Al Bakri Abdullah ◽  
Wan Mastura Wan Ibrahim ◽  
Kamarudin Hussin ◽  
Fakhryna Hannanee Ahmad Zaidi ◽  
...  

The primary motivation of developing ceramic materials using geopolymer method is to minimize the reliance on high sintering temperatures. The ultra-high molecular weight polyethylene (UHMWPE) was added as binder and reinforces the nepheline ceramics based geopolymer. The samples were sintered at 900 °C, 1000 °C, 1100 °C, and 1200 °C to elucidate the influence of sintering on the physical and microstructural properties. The results indicated that a maximum flexural strength of 92 MPa is attainable once the samples are used to be sintered at 1200 °C. It was also determined that the density, porosity, volumetric shrinkage, and water absorption of the samples also affected by the sintering due to the change of microstructure and crystallinity. The IR spectra reveal that the band at around 1400 cm−1 becomes weak, indicating that sodium carbonate decomposed and began to react with the silica and alumina released from gels to form nepheline phases. The sintering process influence in the development of the final microstructure thus improving the properties of the ceramic materials.


2000 ◽  
Vol 14 (1) ◽  
pp. 69-75 ◽  
Author(s):  
G.D. Offner ◽  
R.F. Troxler

The existence of high-molecular-weight glycoproteins in saliva and salivary secretions has been recognized for nearly 30 years. These proteins, called mucins, are essential for oral health and perform many diverse functions in the oral cavity. Mucins have been intensively studied, and much has been learned about their biochemical properties and their interactions with oral micro-organisms and other salivary proteins. In the past several years, the major high-molecular-weight mucin in salivary secretions has been identified as MUC5B, one of a family of 11 human mucin gene products expressed in tissue-specific patterns in the gastrointestinal, respiratory, and reproductive tracts. MUC5B is one of four gel-forming mucins which exist as multimeric proteins with molecular weights greater than 20-40 million daltons. The heavily glycosylated mucin multimers form viscous layers which protect underlying epithelial surfaces from microbial, mechanical, and chemical assault. Another class of mucin molecules, the membrane-bound mucins, is structurally and functionally distinct from the gel-forming mucins. These proteins do not form multimers and can exist as both secreted and membrane-bound forms, with the latter anchored to epithelial cell membranes through a short membrane-spanning domain. In the present work, we show that two of the membrane-bound mucins, MUC1 and MUC4, are expressed in all major human salivary glands as well as in buccal epithelial cells. While the functions of these mucins in the oral environment are not understood, it is possible that they form a structural framework on the cell surface which not only is cytoprotective, but also may serve as a scaffold upon which MUC5B, and possibly other salivary proteins, assemble.


2021 ◽  
Vol 118 (48) ◽  
pp. e2112107118
Author(s):  
Eduardo M. Bruch ◽  
Pierre Vilela ◽  
Lu Yang ◽  
Alexandra Boyko ◽  
Norik Lexa-Sapart ◽  
...  

α-oxoacid dehydrogenase complexes are large, tripartite enzymatic machineries carrying out key reactions in central metabolism. Extremely conserved across the tree of life, they have been, so far, all considered to be structured around a high–molecular weight hollow core, consisting of up to 60 subunits of the acyltransferase component. We provide here evidence that Actinobacteria break the rule by possessing an acetyltranferase component reduced to its minimally active, trimeric unit, characterized by a unique C-terminal helix bearing an actinobacterial specific insertion that precludes larger protein oligomerization. This particular feature, together with the presence of an odhA gene coding for both the decarboxylase and the acyltransferase domains on the same polypetide, is spread over Actinobacteria and reflects the association of PDH and ODH into a single physical complex. Considering the central role of the pyruvate and 2-oxoglutarate nodes in central metabolism, our findings pave the way to both therapeutic and metabolic engineering applications.


2020 ◽  
Vol 27 ◽  
pp. 2169-2173
Author(s):  
B. Suresha ◽  
B. Harshavardhan ◽  
Ashwij M. Rao ◽  
U.R. Koushik ◽  
R. Hemanth

2007 ◽  
Vol 45 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Akiyoshi Sakai ◽  
Sumio Akifusa ◽  
Naoki Itano ◽  
Koji Kimata ◽  
Taro Kawamura ◽  
...  

2005 ◽  
Vol 16 (10) ◽  
pp. 4745-4754 ◽  
Author(s):  
Daniel M. Meyer ◽  
Pascal Crottet ◽  
Bohumil Maco ◽  
Elena Degtyar ◽  
Dan Cassel ◽  
...  

The mechanism of AP-1/clathrin coat formation was analyzed using purified adaptor proteins and synthetic liposomes presenting tyrosine sorting signals. AP-1 adaptors recruited in the presence of Arf1·GTP and sorting signals were found to oligomerize to high-molecular-weight complexes even in the absence of clathrin. The appendage domains of the AP-1 adaptins were not required for oligomerization. On GTP hydrolysis induced by the GTPase-activating protein ArfGAP1, the complexes were disassembled and AP-1 dissociated from the membrane. AP-1 stimulated ArfGAP1 activity, suggesting a role of AP-1 in the regulation of the Arf1 “GTPase timer.” In the presence of cytosol, AP-1 could be recruited to liposomes without sorting signals, consistent with the existence of docking factors in the cytosol. Under these conditions, however, AP-1 remained monomeric, and recruitment in the presence of GTP was short-lived. Sorting signals allowed stable recruitment and oligomerization also in the presence of cytosol. These results suggest a mechanism whereby initial assembly of AP-1 with Arf1·GTP and ArfGAP1 on the membrane stimulates Arf1 GTPase activity, whereas interaction with cargo induces oligomerization and reduces the rate of GTP hydrolysis, thus contributing to efficient cargo sorting.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20504-20504
Author(s):  
B. Rikhof ◽  
J. van Doorn ◽  
A. Suurmeijer ◽  
M. Rautenberg ◽  
P. Jager ◽  
...  

20504 Background: Non-islet cell tumor induced hypoglycemia (NICTH) has been reported anecdotically in patients with a GIST and is associated with increased plasma levels of ‘big’-IGF-II, a high molecular weight form of IGF-II. The role of IGF-II in GIST is unknown. In non- GIST cancer, it has been suggested to be an autocrine growth factor, mainly acting by its major growth promoting receptors IGF-1 receptor (IGF- 1R) and the isoform A of the insulin receptor (IR). We investigated the clinical and biological relevance of (‘big’-)IGF-II in GIST. Methods: Plasma levels of ‘big’-IGF-II, and their relationship with disease status and NICTH, were determined in 25 consecutive GIST patients treated with imatinib (n=24) or sunitinib (n=1). Plasma samples were collected prior to, 1 week, and median 5 months after start of treatment. The levels of ‘big’-IGF-II were measured by specific radioimmunoassay (RIA). Results were compared with those obtained from healthy subjects and expressed as standard deviation scores (SDS). Paraffin-embedded GISTs (n=69) were analyzed for IGF-II, IGF-1R and IR expression by RNA in situ hybridization and immunohistochemistry (IHC). IGF-II secretion by the GIST882 cell line was analyzed by ELISA and western blotting. Results: Before treatment and/or during follow-up, 4 of 25 patients (16%) showed increased (i.e. SDS >2.0) plasma levels of ‘big’-IGF-II. Three of them developed NICTH. Patients with metastatic disease, high serum LDH, or total tumor size >12 cm had the highest ‘big’-IGF-II levels (for all p<0.05). 87% of GISTs expressed IGF-II mRNA, being excessive in tumors from patients with NICTH. These results were confirmed by IHC. GIST882 cells secreted mainly high molecular weight forms of IGF-II. The various GISTs and GIST882 cells did not express IGF-1R or IR. Conclusions: NICTH seems not to be a rare phenomenon in GIST patients. We showed for the first time that most GISTs express and secrete (‘big’-)IGF-II. Therefore, it is likely that many patients are at risk of developing NICTH, presumably especially in case of high tumor bulk. The exact role of (‘big’-)IGF-II in GIST is still not elucidated, as it does not seem to act as an autocrine growth factor since IGF-IR and IR isoform A are lacking. No significant financial relationships to disclose.


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