scholarly journals HIV-Infected Patients: Cross Site-Specific Hydrolysis of H2a and H2b Histones and Myelin Basic Protein with Antibodies against These Three Proteins

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1501
Author(s):  
Svetlana V. Baranova ◽  
Pavel S. Dmitrienok ◽  
Valentina N. Buneva ◽  
Georgy A. Nevinsky
Keyword(s):  
Autoimmune Diseases ◽  
Myelin Basic Protein ◽  
Myelin Sheath ◽  
Cell Apoptosis ◽  
Basic Protein ◽  
Maldi Mass Spectrometry ◽  
Cross Reactivity ◽  
Cleavage Sites ◽  
Negative Role ◽  
Hydrolysis Of

Anti-DNA antibodies are usually produced against histone-DNA complexes appearing during cell apoptosis, while histones are known as damage-associated molecules. A myelin sheath of axons contains myelin basic protein (MBP) playing an important role in the pathogenesis of autoimmune diseases. Antibodies with enzymatic activities (abzymes) are distinctive features of some autoimmune and viral diseases. Abzymes against different proteins can usually only hydrolyze these specific proteins. Using sequential chromatographies of homogeneous IgG preparations from sera of HIV-infected patients on columns with immobilized MBP, H2a, and H2b histones, the anti-MBP, anti-H2a, and anti-H2b antibodies were obtained. It was first shown that IgGs against H2a and H2b effectively hydrolyze these histones and MBP, while anti-MBP split MBP, H2a, and H2b, but no other control proteins. Using the MALDI mass spectrometry, the cleavage sites of H2a, H2b, and MBP by abzymes against these three proteins were found. Among 14 sites of hydrolysis of H2a by IgGs against H2a and 10 sites by anti-MBP IgGs, only one site of hydrolysis was the same for these abzymes. Eleven cleavage sites of H2b with IgGs against H2b and 10 sites of its hydrolysis with antibodies against MBP were different. Anti-H2a, anti-H2b, and anti-MBP abzymes are unpredictable examples of IgGs possessing not only cross-complexation but also catalytic cross-reactivity, which may be a common phenomenon for such abzymes in patients with different autoimmune diseases. The existence of cross-reactivity of abzymes against H2a and H2b histones and MBP represent a great danger to humans since, in contrast with MBP, histones due to cell apoptosis constantly occur in human blood. Anti-H2a, anti-H2b, and anti-MBP can attack and hydrolyze myelin basic protein of the myelin sheath of axons and plays a negative role in the pathogenesis of several pathologies.

scholarly journals HIV-Infected Patients: Cross Site-Specific Hydrolysis of H3 and H4 Histones and Myelin Basic Protein with Antibodies against These Three Proteins

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 316
Author(s):  
Svetlana V. Baranova ◽  
Pavel S. Dmitrenok ◽  
Valentina N. Buneva ◽  
Sergey E. Sedykh ◽  
Georgy A. Nevinsky
Keyword(s):  
Myelin Basic Protein ◽  
Intercellular Space ◽  
Basic Protein ◽  
Cross Reactivity ◽  
Cleavage Sites ◽  
Site Specific ◽  
Protein Clusters ◽  
Negative Role ◽  
Toxic Responses ◽  
Hydrolysis Of

Histones play important roles in chromatin functioning and gene transcription, but in the intercellular space, they are harmful since they stimulate systemic inflammatory and toxic responses. Electrophoretically homogeneous IgGs against myelin basic protein (MBP), as well as H3 and H4 histones, were isolated from sera of HIV-infected patients. In contrast to known classical proteases, these IgGs split exclusively only histones and MBP but no other control proteins. Among 13 sites of hydrolysis of H3 by IgGs against H3 and 14 sites for anti-MBP IgGs, only two sites of the hydrolysis were the same. Between seven cleavage sites of H4 with IgGs against H4 and 9 sites of this histone hydrolysis by antibodies against MBP, only three sites were the same. The sites of hydrolysis of H3 (and H4) with abzymes against these histones and against MBP were different, but several expended protein clusters containing hydrolysis sites are partially overlapped. The existence of enzymatic cross-reactivity of abzymes against H3 and H4 and MBP represents a great menace to humans since due to cell apoptosis, histones constantly occur in human blood. They can hydrolyze MBP of the myelin sheath of axons and play a negative role in the pathogenesis of HIV-infected patients.

scholarly journals Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1140
Author(s):  
Georgy A. Nevinsky ◽  
Svetlana V. Baranova ◽  
Valentina N. Buneva ◽  
Pavel S. Dmitrenok
Keyword(s):  
Multiple Sclerosis ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Maldi Mass Spectrometry ◽  
High Rate ◽  
H1 Histone ◽  
Constituent Element ◽  
Negative Role ◽  
Rate Of Hydrolysis ◽  
Hydrolysis Of

Histones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the myelin-proteolipid sheath of axons. Abzymes (antibodies with catalytic activities) are the original features of some autoimmune diseases. In this study, electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, and H4 histones and myelin basic protein (MBP) were isolated from the blood sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI mass spectrometry, the sites of H1 histone cleavage by IgGs against H1, H2A, H2B, H3, H4, and MBP were determined. It was shown that IgGs against H1 split H1 at 12 sites, while the number of cleavage sites by abzymes against other histones was lower: H2A (9), H2B (7), H3 (3), and H4 (3). The minimum rate of H1 hydrolysis was observed for antibodies against H3 and H4. A high rate of hydrolysis and the maximum number of H1 hydrolysis sites (17) were found for antibodies against MBP. Only a few sites of H1 hydrolysis by anti-H1 antibodies coincided with those for IgGs against H2A, H2B, H3, H4, and MBP. Thus, the polyreactivity of complexation and the enzymatic cross-activity of antibodies against H1, four other histones, and MBP have first been shown. Since histones act as damage molecules, abzymes against histones and MBP can play a negative role in the pathogenesis of MS and probably other different diseases as well.

scholarly journals Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 630 ◽  
Author(s):  
Irina A. Kostrikina ◽  
Valentina N. Buneva ◽  
Enrico Granieri ◽  
Georgy A. Nevinsky
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Relative Concentration ◽  
Correlation Coefficients ◽  
Hydrolysis Of ◽  
Hydrolysis Of Dna

It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.

scholarly journals Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K

2011 ◽  
Vol 192 (5) ◽  
pp. 797-811 ◽  
Author(s):  
Lisbeth S. Laursen ◽  
Colin W. Chan ◽  
Charles ffrench-Constant
Keyword(s):  
Protein Synthesis ◽  
Myelin Basic Protein ◽  
Myelin Sheath ◽  
Basic Protein ◽  
Inhibitory Effect ◽  
Integrin Activation ◽  
Hnrnp K ◽  
Sheath Formation ◽  
The Central Nervous System ◽  
Mrna Binding

Myelination in the central nervous system provides a unique example of how cells establish asymmetry. The myelinating cell, the oligodendrocyte, extends processes to and wraps multiple axons of different diameter, keeping the number of wraps proportional to the axon diameter. Local regulation of protein synthesis represents one mechanism used to control the different requirements for myelin sheath at each axo–glia interaction. Prior work has established that β1-integrins are involved in the axoglial interactions that initiate myelination. Here, we show that integrin activation regulates translation of a key sheath protein, myelin basic protein (MBP), by reversing the inhibitory effect of the mRNA 3′UTR. During oligodendrocyte differentiation and myelination α6β1-integrin interacts with hnRNP-K, an mRNA-binding protein, which binds to MBP mRNA and translocates from the nucleus to the myelin sheath. Furthermore, knockdown of hnRNP-K inhibits MBP protein synthesis during myelination. Together, these results identify a novel pathway by which axoglial adhesion molecules coordinate MBP synthesis with myelin sheath formation.

scholarly journals T cell determinants of myelin basic protein include a unique encephalitogenic I-E-restricted epitope for Lewis rats.

1989 ◽  
Vol 170 (2) ◽  
pp. 355-367 ◽  
Author(s):  
H Offner ◽  
G A Hashim ◽  
B Celnik ◽  
A Galang ◽  
X B Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Guinea Pig ◽  
Autoimmune Diseases ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Lewis Rats ◽  
Gene Combination ◽  
First Time ◽  
Restricted Epitope

The major encephalitogenic epitope for Lewis rats is the 72-89 sequence of guinea pig basic protein (GP-BP) or rat basic protein (Rt-BP). T cells responsive to this epitope are I-A restricted and preferentially express the V alpha 2:V beta 8 gene combination in their TCR. In this work, we describe for the first time the delayed appearance of T cells specific for additional discrete determinant of BP, the nonencephalitogenic 55-68 sequence of GP-BP restricted by I-A, and the encephalitogenic 87-99 sequence of Rt-BP restricted by I-E. The TCR V alpha 2:V beta 8 gene combination was expressed by both encephalitogenic GP-BP S72-89 and Rt-BP S87-99 T cell specificities but not by GP-BP 44-68-specific T cells. This is the first demonstration of I-E-restricted encephalitogenic T cells in Lewis rats and supports the conclusion that the I-E class II locus is involved in autoimmune diseases.

Sign in / Sign up

Export Citation Format

Share Document