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EAE of Mice: Enzymatic Cross Site-Specific Hydrolysis of H2B Histone by IgGs against H1, H2A, H2B, H3, and H4 Histones and Myelin Basic Protein Full article

Journal Molecules
ISSN: 1420-3049
Output data Year: 2023, Volume: 28, Number: 7, Article number : 29738, Pages count : DOI: 10.3390/molecules28072973
Authors Urusov A.E. 1 , Aulova K.S. 1 , Dmitrenok P.S. 2 , Buneva V.N. 1 , Nevinsky G.A. 1
Affiliations
1 Institute of Chemical Biology and Fundamental Medicine SB RAS
2 G. B. Elyakov Pacific Institute of Bioorganic Chemistry, Far East Division, Russian Academy of Sciences, Vladivostok, 690,022, Russian Federation

Funding (1)

1 Russian Science Foundation РНФ №22-15-00103

Abstract: Histones have vital roles in chromatin functioning and gene transcription. At the same time, they are pernicious in intercellular space because they stimulate systemic inflammatory and toxic responses. Myelin basic protein (MBP) is the major protein of the axon myelin–proteolipid sheath. Antibody-abzymes with various catalytic activities are specific features of some autoimmune diseases. IgGs against five individual histones (H2B, H1, H2A, H3, and H4) and MBP were isolated from the blood of experimental autoimmune encephalomyelitis-prone C57BL/6 mice by affinity chromatography. Abzymes corresponding to various stages of EAE development, including spontaneous EAE, myelin oligodendrocyte glycoprotein (MOG)- and DNA-histone complex-accelerated onset, as well as acute and remission stages, were analyzed. IgG-abzymes against MBP and five individual histones showed unusual polyreactivity in complex formation and enzymatic cross-reactivity in the specific hydrolysis of H2B histone. All IgGs against MBP and individual histones in 3-month-old mice (zero time) demonstrated from 4 to 11 different H2B hydrolysis sites. Spontaneous development of EAE during 60 days led to a significant change in the type and number of H2B hydrolysis sites by IgGs against the five histones and MBP. Mouse treatment with MOG and DNA-histone complex changed the type and number of H2B hydrolysis sites compared to zero time. The minimum number (3) of different H2B hydrolysis sites was found for IgGs against H3 20 days after mouse immunization with DNA-histone complex, whereas the maximum number (33) for anti-H2B IgGs was found 60 days after mouse treatment with DNA-histone complex. Overall, this is the first study to demonstrate that at different stages of EAE evolution, IgG-abzymes against five individual histones and MBP could significantly differ in the specific sites and number of H2B hydrolysis sites. Possible reasons for the catalytic cross-reactivity and significant differences in the number and type of histone H2B cleavage sites were analyzed.
Cite: Urusov A.E. , Aulova K.S. , Dmitrenok P.S. , Buneva V.N. , Nevinsky G.A.
EAE of Mice: Enzymatic Cross Site-Specific Hydrolysis of H2B Histone by IgGs against H1, H2A, H2B, H3, and H4 Histones and Myelin Basic Protein
Molecules. 2023. V.28. N7. 29738 . DOI: 10.3390/molecules28072973 WOS Scopus РИНЦ OpenAlex
Dates:
Published print: Mar 27, 2023
Identifiers:
Web of science: WOS:000968723600001
Scopus: 2-s2.0-85160375400
Elibrary: 50416458
OpenAlex: W4361007788
Citing:
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Elibrary 4
OpenAlex 4
Web of science 3
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