Dicarbonyl Induced Structural Perturbations Make Histone H1 Highly Immunogenic and Generate an Auto-Immune Response in Cancer

PloS One
Abdul Rouf MirAsif Ali

Abstract

Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG) and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm) studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified ...Continue Reading

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Citations

Feb 11, 2016·International Journal of Biological Macromolecules· Jyoti Moinuddin
Jan 24, 2016·International Journal of Biological Macromolecules·Farzana KhanAsif Ali
Dec 15, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Abdul Rouf MirSidra Islam
Dec 29, 2016·International Journal of Biological Macromolecules·Abdul Rouf MirSafia Habib
Aug 11, 2017·Journal of Biomolecular Structure & Dynamics·Sidra IslamAsif Ali
Jun 20, 2019·Biochemistry. Biokhimii︠a︡·O V KosmachevskayaA F Topunov
Feb 9, 2021·Glycobiology·Abdul Rouf MirMoin Uddin
Mar 11, 2021·Free Radical Biology & Medicine·José-Luis García-GiménezFederico V Pallardó
Jan 10, 2019·International Journal of Biological Macromolecules·Shahida Perween Moinuddin

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Methods Mentioned

BETA
ELISA
fluorescence spectroscopy
circular dichroism
Scanning Electron Microscopy
glycosylation
X-ray

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