Amorphous aggregate adducts of linker histone H1 turn highly immunologic in the cancers of oesophagus, stomach, gall bladder and ovary

作者：Mir Abdul Rouf; Moinuddin; Habib Safia

来源：International Journal of Biological Macromolecules, 2017, 96: 507-517.

DOI：10.1016/j.ijbiomac.2016.12.060

• Histone glycoxidation
• Circulating auto antibodies
• Cancer

Hyperglycaemic influence on carcinogenesis and tumour progression is emerging as a link between diabetes and cancer. This work establishes the disturbed structural integrity of nucleosomal linker histone H1 by methyglyoxal (MG) and then correlates the role of modified H1 in the auto-immunopathogenesis of multiple cancers. MG modification caused a loss of free epsilon-amino groups in H1 and raised its beta-sheet structural component with a consequence of non amyloid aggregation. It changed the folding-unfolding denaturation pattern of H1 and attached itself to the lysine residues of the protein eventually making up N-epsilon-(carboxyethyl) lysine. The structural variations act as extra antigenic determinants on H1 that yield aggressive antibody response, when immunised in rabbits. The ELISA tests proved the immunoglobulin response very specific and gel based studies established the preferential binding of antibodies generated against MG-H1 with the modified protein. Cross reaction analysis inferred the multiple specific natures of immunoglobulins with binding tendencies against different inhibitors. The immunoglobulin content in blood sera derived from human subjects with tumours of oesophagus, stomach, gall bladder and ovary confirmed the antibody presence against MG-H1 and competitive ELISA showed their high specificity. This may suggest a link between nucleosomal linker H1, hyperglycaemia, glycoxidation and cancer.

• 出版日期2017-3