PMID- 28583871
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20180430
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 104
IP  - Pt A
DP  - 2017 Nov
TI  - Studies on glycoxidatively modified human IgG: Implications in immuno-pathology 
      of type 2 diabetes mellitus.
PG  - 19-29
LID - S0141-8130(17)30174-5 [pii]
LID - 10.1016/j.ijbiomac.2017.05.190 [doi]
AB  - Structural rearrangements and condensations of proteins under hyperglycemic 
      stress have been implicated in various pathological disorders. This study aims to 
      probe the role of methylglyoxal (MG) modified human immunoglobulin G (MG-IgG) in 
      immuno-pathology of type 2 diabetes mellitus (T2DM). MG was found to perturb the 
      structural integrity of IgG, affect its aromatic micro-environment and cause the 
      generation of advanced glycation end products (AGEs) and aggregate adducts. It 
      liberated the hydrophobic pockets of the protein, reduced its beta pleated sheet 
      structure and affected its tertiary conformation. Transition from beta sheet to alpha 
      helix and random coil was also observed in IgG upon modification by MG. It acted 
      with strong oxidative potential and caused oligomerisation and disordered or 
      amorphous type aggregation in the modified protein. Modified IgG had a cytotoxic 
      and genotoxic impact. The MG modified IgG presented novel antigenic determinants 
      that lead to an aggressive immune response. The antibodies had high affinity 
      towards the immunogen. Auto-antibodies derived from T2DM patients exhibited 
      strong affinity towards the modified IgG in comparison to the unmodified protein. 
      Specificity of serum antibodies from T2DM patients was further confirmed by 
      competitive-inhibition ELISA. The potential role of MG-IgG in the 
      immunopathogenesis of T2DM has been discussed.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Islam, Sidra
AU  - Islam S
AD  - Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, 
      Aligarh 202002, U.P., India.
FAU - Moinuddin
AU  - Moinuddin
AD  - Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, 
      Aligarh 202002, U.P., India. Electronic address: moinuddin.bh@amu.ac.in.
FAU - Mir, Abdul Rouf
AU  - Mir AR
AD  - Department of Biotechnology, Government Degree College Baramulla, University of 
      Kashmir, 193101, Jammu and Kashmir, India.
FAU - Arfat, Mir Yasir
AU  - Arfat MY
AD  - Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, 
      Aligarh 202002, U.P., India.
FAU - Alam, Khursheed
AU  - Alam K
AD  - Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, 
      Aligarh 202002, U.P., India.
FAU - Ali, Asif
AU  - Ali A
AD  - Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, 
      Aligarh 202002, U.P., India.
LA  - eng
PT  - Journal Article
DEP - 20170603
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Immunoglobulin G)
RN  - 722KLD7415 (Pyruvaldehyde)
SB  - IM
MH  - DNA Damage
MH  - Diabetes Mellitus, Type 2/genetics/*immunology/metabolism
MH  - Glycation End Products, Advanced/metabolism
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunoglobulin G/*metabolism
MH  - Lymphocytes/metabolism
MH  - Pyruvaldehyde/*metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - Autoimmunity
OT  - Glycation
OT  - Immunoglobulin G
OT  - Methylglyoxal
OT  - Type 2 diabetes mellitus
EDAT- 2017/06/07 06:00
MHDA- 2018/05/01 06:00
CRDT- 2017/06/07 06:00
PHST- 2017/01/12 00:00 [received]
PHST- 2017/05/31 00:00 [accepted]
PHST- 2017/06/07 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2017/06/07 06:00 [entrez]
AID - S0141-8130(17)30174-5 [pii]
AID - 10.1016/j.ijbiomac.2017.05.190 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2017 Nov;104(Pt A):19-29. doi: 
      10.1016/j.ijbiomac.2017.05.190. Epub 2017 Jun 3.