Abdul Rouf Mir
Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, AMU, Aligarh, Uttar Pradesh, India
Title: Glycoxidation mediated amorphous aggregation of linker histone H1 generates specific auto-antibodies in patients with cancer of lungs and prostate.
Biography
Biography: Abdul Rouf Mir
Abstract
Aberrant non enzymatic protein modifications under glycoxidation and AGE-RAGE axis
have emerged as a promising research in the field of cancer. Glycoxdiation makes proteins
immunogenic and stimulates specific humoral immune responses. We studied methylglyoxal
induced H1 histone modifications and their role in immunopathology of cancer. We observed
lysine side chain modifications, blocking of free amino groups and the formation of
condensed cross structures in histone H1. It generated N
É›
-(carboxyethyl) lysine (CEL) as
observed in MALDI-MS, HPLC and LCMS. MG-H1 appeared as an amorphous aggregate
under electron microscopy and gave altered binding with DNA in CD studies. The modified
histone elicited high titre immunogen specific antibodies in rabbits when compared to the
native, thus pointing towards the generation of neo-epitopes in MG-H1. The auto-antibodies
derived from cancer patients exhibited enhanced binding with MG-H1 as compared to the
native histone in ELISA, gel retardation assay and Western blot analysis. MG-1 may be
considered as potential antigenic candidate for autoimmune response in cancer with potential
role as a biomarker for early detection of cancers.