NDLI: Interaction of glycated protein and DFO mimicked hypoxia in cellular responses of HUVECs.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bala, Kanchan Gohil, Nivedita Karmakar
Description	Country affiliation: India Author Affiliation: Bala K ( Centre for Biomedical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi 110 016, India. nkarm@yahoo.com)
Abstract	The accelerated non-enzymatic modification of proteins by Maillard reaction during prolonged hyperglycemia is a key player in the diabetes associated pathology. In addition, hypoxia has been implicated in the recent past as a modulating factor. Therefore we have examined the interaction of glycation modified human serum albumin (AGE-HSA) and deferoxamine (DFO) mimicked hypoxia on the expression of hypoxia inducible factor 1 (HIF-1 ), and the role of RAGE (receptor for AGE) signaling in up-regulation of HIF-1 . Expression of VEGF (a downstream target of HIF-1 ) and sICAM-1 (inflammatory marker) was also detected. When HUVEC were subjected to hypoxia, highest expression of HIF-1 was observed. When treated with AGE-HSA at two concentrations, higher expression was found vis-a-vis control, with 0.2 mg ml(-1) than 2.0 mg ml(-1) which was mediated in part by RAGE as determined by RAGE silencing. However, when the cells were exposed to a combination treatment of hypoxia and AGE-HSA, a biphasic effect at the two different concentrations was observed as compared to the individual treatments. VEGF was synergistically up-regulated by hypoxia and AGE-HSA. On the other hand sICAM-1 was up-regulated by AGE-HSA but down-regulated by hypoxia. These results show that AGE-HSA functions as a non-hypoxic factor which modulates the expression of HIF-1 in a concentration dependent manner in the range studied. It can be concluded that glycated serum proteins may activate HIF-1 independently in diabetes. Further, when both glycated proteins and hypoxic conditions are present, they act in opposition in regulation of HIF-1 .
File Format	HTM / HTML
ISSN	1742206X
Issue Number	10
Volume Number	8
e-ISSN	17422051
Journal	Molecular BioSystems
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2012-10-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Deferoxamine Pharmacology Glycosylation End Products, Advanced Oxygen Serum Albumin Advanced Glycosylation End Product-specific Receptor Dose-response Relationship, Drug Drug Combinations Female Gene Expression Drug Effects Human Umbilical Vein Endothelial Cells Humans Anoxia Metabolism Hypoxia-inducible Factor 1, Alpha Subunit Genetics Immunohistochemistry Intercellular Adhesion Molecule-1 Models, Biological Rna, Small Interfering Receptors, Immunologic Antagonists & Inhibitors Signal Transduction Vascular Endothelial Growth Factor A Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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