scholarly journals Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes

1987 ◽  
Vol 245 (1) ◽  
pp. 243-250 ◽  
Author(s):  
S P Wolff ◽  
R T Dean
Keyword(s):  
Protein Modification ◽  
Potential Role ◽  
Chelating Agent ◽  
Tryptophan Fluorescence ◽  
Protein Glycosylation ◽  
Covalent Attachment ◽  
Amino Groups ◽  
Tryptophan Fluorescence Quenching

Monosaccharide autoxidation (a transition metal-catalysed process that generates H2O2 and ketoaldehydes) appears to contribute to protein modification by glucose in vitro. The metal-chelating agent diethylenetriaminepenta-acetic acid (DETAPAC), which inhibits glucose autoxidation, also reduces the covalent attachment of glucose to bovine serum albumin. A maximal 45% inhibition of covalent attachment was observed, but this varied with glucose and DETAPAC concentrations in a complex fashion, suggesting at least two modes of attachment. The extent of inhibition of the metal-catalysed pathway correlated with the extent of inhibition of glycosylation-associated chromo- and fluorophore development. DETAPAC also inhibited tryptophan fluorescence quenching associated with glycosylation. Conversely, ketoaldehydes analogous to those produced by glucose autoxidation, but generated by 60Co irradiation, bound avidly to albumin and accelerated browning reactions. It is therefore suggested that a component of protein glycosylation is dependent upon glucose autoxidation and subsequent covalent attachment of ketoaldehydes. The process of glucose autoxidation, or ketoaldehydes derived therefrom, appear to be important in chromophoric and fluorophoric alterations. It is noted, consistent with these observations, that the chemical evidence for the currently accepted ‘Amadori’ product derived from the reaction of glucose with protein amino groups is consistent also with the structure expected for the attachment of a glucose-derived ketoaldehyde to protein. The concept of ‘autoxidative glycosylation’ is briefly discussed in relation to oxidative stress in diabetes mellitus.

scholarly journals The development of a molecular toolbox to examine the role of protein O-mannosylation in actinobacteria

2021 ◽  
Author(s):  
Nakita Buenbrazo
Keyword(s):  
Functional Role ◽  
Protein Modification ◽  
Cell Function ◽  
Protein Glycosylation ◽  
Covalent Attachment ◽  
Cell Defense ◽  
Domains Of Life ◽  
Cell Processes

Protein glycosylation is the most abundant and diverse protein modification that occurs in all domains of life. It is defined as the covalent attachment of a carbohydrate moiety to a specific amino acid on a target protein. The functional role of this attachment is implicated in and spans various cell processes from cell signaling, cell defense, and pathogenesis – to name a few. A specific type of protein glycosylation, called protein O-mannosylation (POM) is a process found to be conserved from bacteria to man. In humans, POM is required for healthy cell function, and the absence of POM can cause fatal diseases. Certain prokaryotic species possess a related POM system, but it is poorly understood. It is our hypothesis that the analysis of the POM system in simpler organisms can aid in the characterization of this process and the functional role of the mannosylated proteins that are produced. However, the protocols to prove this theory do not yet exist. This thesis establishes a collection of developed protocols that can be used to characterize the POM systems from gram-positive species Corynebacterium glutamicum and Cellulomonas fimi. In addition the first ever evidence of a C. fimi glycoprotein being glycosylated by the endogenous C. glutamicum POM system is provided.

scholarly journals The development of a molecular toolbox to examine the role of protein O-mannosylation in actinobacteria

2021 ◽  
Author(s):  
Nakita Buenbrazo
Keyword(s):  
Functional Role ◽  
Protein Modification ◽  
Cell Function ◽  
Protein Glycosylation ◽  
Covalent Attachment ◽  
Cell Defense ◽  
Domains Of Life ◽  
Cell Processes

Protein glycosylation is the most abundant and diverse protein modification that occurs in all domains of life. It is defined as the covalent attachment of a carbohydrate moiety to a specific amino acid on a target protein. The functional role of this attachment is implicated in and spans various cell processes from cell signaling, cell defense, and pathogenesis – to name a few. A specific type of protein glycosylation, called protein O-mannosylation (POM) is a process found to be conserved from bacteria to man. In humans, POM is required for healthy cell function, and the absence of POM can cause fatal diseases. Certain prokaryotic species possess a related POM system, but it is poorly understood. It is our hypothesis that the analysis of the POM system in simpler organisms can aid in the characterization of this process and the functional role of the mannosylated proteins that are produced. However, the protocols to prove this theory do not yet exist. This thesis establishes a collection of developed protocols that can be used to characterize the POM systems from gram-positive species Corynebacterium glutamicum and Cellulomonas fimi. In addition the first ever evidence of a C. fimi glycoprotein being glycosylated by the endogenous C. glutamicum POM system is provided.

scholarly journals Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1092
Author(s):  
János András Mótyán ◽  
Márió Miczi ◽  
Stephen Oroszlan ◽  
József Tőzsér
Keyword(s):  
Amino Acid ◽  
Zinc Finger ◽  
Cleavage Site ◽  
Potential Role ◽  
Binding Mode ◽  
Interaction Energies ◽  
Vitro Assay ◽  
Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

scholarly journals High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun-Qian Cui ◽  
Fei Meng ◽  
Wen-Li Zhan ◽  
Zhou-Tong Dai ◽  
Xinghua Liao
Keyword(s):  
Potential Role ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
High Expression ◽  
Poor Survival ◽  
Free Survival

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.

scholarly journals Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Bernardino Clavo ◽  
Norberto Santana-Rodríguez ◽  
Pedro Llontop ◽  
Dominga Gutiérrez ◽  
Gerardo Suárez ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Immune Modulation ◽  
Animal Studies ◽  
Potential Role ◽  
Randomized Clinical Trials ◽  
Tumor Hypoxia ◽  
Tumor Resection ◽  
Ozone Therapy

Introduction. This article provides an overview of the potential use of ozone as an adjuvant during cancer treatment.Methods. We summarize the findings of the most relevant publications focused on this goal, and we include our related clinical experience.Results. Over several decades, prestigious journals have publishedin vitrostudies on the capacity of ozone to induce direct damage on tumor cells and, as well, to enhance the effects of radiotherapy and chemotherapy. Indirect effects have been demonstrated in animal models: immune modulation by ozone alone and sensitizing effect of radiotherapy by concurrent ozone administration. The effects of ozone in modifying hemoglobin dissociation curve, 2,3-diphosphoglycerate levels, locoregional blood flow, and tumor hypoxia provide additional support for potential beneficial effects during cancer treatment. Unfortunately, only a few clinical studies are available. Finally, we describe some works and our experience supporting the potential role of local ozone therapy in treating delayed healing after tumor resection, to avoid delays in commencing radiotherapy and chemotherapy.Conclusions.In vitroand animal studies, as well as isolated clinical reports, suggest the potential role of ozone as an adjuvant during radiotherapy and/or chemotherapy. However, further research, such as randomized clinical trials, is required to demonstrate its potential usefulness as an adjuvant therapeutic tool.

scholarly journals Potential Role of the Chemokine Macrophage Inflammatory Protein 1α in Human and Experimental Schistosomiasis

2005 ◽  
Vol 73 (4) ◽  
pp. 2515-2523 ◽  
Author(s):  
Adriano L. S. Souza ◽  
Ester Roffê ◽  
Vanessa Pinho ◽  
Danielle G. Souza ◽  
Adriana F. Silva ◽  
...  
Keyword(s):  
Potential Role ◽  
Severe Disease ◽  
Experimental Studies ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein ◽  
Deficient Mice

ABSTRACT In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1α (MIP-1α/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.

scholarly journals Role for the Related Poly(ADP-Ribose) Polymerases Tankyrase 1 and 2 at Human Telomeres

2002 ◽  
Vol 22 (1) ◽  
pp. 332-342 ◽  
Author(s):  
Brandoch D. Cook ◽  
Jasmin N. Dynek ◽  
William Chang ◽  
Grigoriy Shostak ◽  
Susan Smith
Keyword(s):  
Potential Role ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Continuous Growth ◽  
Telomere Elongation ◽  
Bona Fide ◽  
Tankyrase 1 ◽  
Growth Of Tumor

ABSTRACT Telomere maintenance is essential for the continuous growth of tumor cells. In most human tumors telomeres are maintained by telomerase, a specialized reverse transcriptase. Tankyrase 1, a human telomeric poly(ADP-ribose) polymerase (PARP), positively regulates telomere length through its interaction with TRF1, a telomeric DNA-binding protein. Tankyrase 1 ADP-ribosylates TRF1, inhibiting its binding to telomeric DNA. Overexpression of tankyrase 1 in the nucleus promotes telomere elongation, suggesting that tankyrase 1 regulates access of telomerase to the telomeric complex. The recent identification of a closely related homolog of tankyrase 1, tankyrase 2, opens the possibility for a second PARP at telomeres. We therefore sought to establish the role of tankyrase 1 at telomeres and to determine if tankyrase 2 might have a telomeric function. We show that endogenous tankyrase 1 is a component of the human telomeric complex. We demonstrate that telomere elongation by tankyrase 1 requires the catalytic activity of the PARP domain and does not occur in telomerase-negative primary human cells. To investigate a potential role for tankyrase 2 at telomeres, recombinant tankyrase 2 was subjected to an in vitro PARP assay. Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres. These findings establish tankyrase 2 as a bona fide PARP, with itself and TRF1 as acceptors of ADP-ribosylation, and suggest the possibility of a role for tankyrase 2 at telomeres.

scholarly journals Malaria and red cell genetic defects

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1213-1221 ◽  
Author(s):  
RL Nagel ◽  
EF Jr Roth
Keyword(s):  
Culture System ◽  
Potential Role ◽  
Dna Analysis ◽  
Red Cell ◽  
Metabolic Products ◽  
Recombinant Technology ◽  
Host Parasite ◽  
Made In

Abstract The study of inherited RBC resistance to malaria has increased our knowledge of the biochemistry and physiology of the host-parasite interaction and suggested potential sites for therapeutic intervention. Discovery by Jensen and Trager of the in vitro culture system for P falciparum has facilitated research in this area. Known RBC defects may affect invasion, growth, or merozoite liberation (Fig 1). Significant advances made in understanding mechanisms underlying protection against malaria should not obscure the fact that the data are far from complete. More knowledge is needed about the influence of the erythrocyte cytoskeleton on invasion and growth of parasites as well as the potential role of phospholipids, erythrocyte enzymes other than G6PD, or other metabolic products. Application of DNA analysis and recombinant technology may have an increasing impact on study of the interaction of RBC defects with malarial parasites.

scholarly journals Intestinal miRNAs regulated in response to dietary lipids

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Judit Gil-Zamorano ◽  
João Tomé-Carneiro ◽  
María-Carmen Lopez de las Hazas ◽  
Lorena del Pozo-Acebo ◽  
M. Carmen Crespo ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lipid Metabolism ◽  
Chronic Exposure ◽  
Potential Role ◽  
In Vitro Models ◽  
Dietary Lipids ◽  
Metabolism Regulation

Abstract The role of miRNAs in intestinal lipid metabolism is poorly described. The small intestine is constantly exposed to high amounts of dietary lipids, and it is under conditions of stress that the functions of miRNAs become especially pronounced. Approaches consisting in either a chronic exposure to cholesterol and triglyceride rich diets (for several days or weeks) or an acute lipid challenge were employed in the search for intestinal miRNAs with a potential role in lipid metabolism regulation. According to our results, changes in miRNA expression in response to fat ingestion are dependent on factors such as time upon exposure, gender and small intestine section. Classic and recent intestinal in vitro models (i.e. differentiated Caco-2 cells and murine organoids) partially mirror miRNA modulation in response to lipid challenges in vivo. Moreover, intestinal miRNAs might play a role in triglyceride absorption and produce changes in lipid accumulation in intestinal tissues as seen in a generated intestinal Dicer1-deletion murine model. Overall, despite some variability between the different experimental cohorts and in vitro models, results show that some miRNAs analysed here are modulated in response to dietary lipids, hence likely to participate in the regulation of lipid metabolism, and call for further research.

The new world of inorganic polyphosphates

2016 ◽  
Vol 44 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Cristina Azevedo ◽  
Adolfo Saiardi
Keyword(s):  
Protein Modification ◽  
Biochemical Characterization ◽  
Covalent Attachment ◽  
Detection Methods ◽  
Inorganic Polyphosphate ◽  
Post Translational Modifications ◽  
Topoisomerase 1 ◽  
Lysine Residues ◽  
Acidic Conditions

Post-translational modifications (PTMs) add regulatory features to proteins that help establish the complex functional networks that make up higher organisms. Advances in analytical detection methods have led to the identification of more than 200 types of PTMs. However, some modifications are unstable under the present detection methods, anticipating the existence of further modifications and a much more complex map of PTMs. An example is the recently discovered protein modification polyphosphorylation. Polyphosphorylation is mediated by inorganic polyphosphate (polyP) and represents the covalent attachment of this linear polymer of orthophosphate to lysine residues in target proteins. This modification has eluded MS analysis as both polyP itself and the phosphoramidate bonds created upon its reaction with lysine residues are highly unstable in acidic conditions. Polyphosphorylation detection was only possible through extensive biochemical characterization. Two targets have been identified: nuclear signal recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1). Polyphosphorylation occurs within a conserved N-terminal polyacidic serine (S) and lysine (K) rich (PASK) cluster. It negatively regulates Nsr1–Top1 interaction and impairs Top1 enzymatic activity, namely relaxing supercoiled DNA. Modulation of cellular levels of polyP regulates Top1 activity by modifying its polyphosphorylation status. Here we discuss the significance of the recently identified new role of inorganic polyP.

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