Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro

Increased oxidative stress (OS) in diabetes mellitus is one of the major factors leading to diabetic pathology. However, the mediators and mechanism that provoke OS in diabetes is not fully understood, and it is possible that accumulation of advanced glycation end products (AGEs) formed secondary to...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2012-02, Vol.361 (1-2), p.289-296
Main Authors: Bansal, Savita, Siddarth, Manushi, Chawla, Diwesh, Banerjee, Basu D., Madhu, S. V., Tripathi, Ashok K.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Cardiology
Diabetes
Enzymes
Glycation End Products, Advanced - pharmacology
Glycation End Products, Advanced - physiology
Humans
Leukocytes
Life Sciences
Lipid Peroxidation
Medical Biochemistry
NADPH Oxidases - metabolism
Neutrophils - enzymology
Neutrophils - metabolism
Neutrophils - physiology
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - metabolism
Oncology
Oxidases
Oxidative Stress
Oxygen
Protein Carbonylation
Proteins
Serum Albumin - chemistry
Superoxides - metabolism
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Summary:Increased oxidative stress (OS) in diabetes mellitus is one of the major factors leading to diabetic pathology. However, the mediators and mechanism that provoke OS in diabetes is not fully understood, and it is possible that accumulation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions may incite circulating polymorphonuclear neutrophils (PMN) to generate reactive oxygen species (ROS). In this report, we aim to investigate the effect of AGE on reactive oxygen and nitrogen species generation and subsequent OS in PMN. AGE-HSA exert dose- and time-dependent enhancement of ROS and reactive nitrogen intermediates (RNI) generation by PMN. Increased ROS and RNI generation were found to be mediated through the upregulation of NADPH oxidase and inducible nitric oxide synthase (iNOS), respectively, as evident from the fact that AGE-treated neutrophils failed to generate ROS and RNI in presence of diphenyleneiodonium, a flavoprotein inhibitor for both enzymes. Further increased generation of ROS and RNI ceased when the cells were incubated with anti-RAGE antibody suggesting the involvement of AGE–RAGE interaction. Also increased malondialdehyde (MDA) and protein carbonyl formation in AGE-exposed PMN suggest induction of OS by AGE. This study provides evidence that AGEs may play a key role in the induction of oxidative stress through the augmentation of PMN-mediated ROS and RNI generation and this may be in part responsible for development of AGE-induced diabetic pathology.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-011-1114-9