PMID- 20227863
OWN - NLM
STAT- MEDLINE
DCOM- 20110719
LR  - 20171116
IS  - 1590-3729 (Electronic)
IS  - 0939-4753 (Linking)
VI  - 21
IP  - 4
DP  - 2011 Apr
TI  - Induction of HO-1 and redox signaling in endothelial cells by advanced glycation 
      end products: a role for Nrf2 in vascular protection in diabetes.
PG  - 277-85
LID - 10.1016/j.numecd.2009.12.008 [doi]
AB  - BACKGROUND AND AIMS: Hyperglycemia and diabetes are associated with increased 
      formation of advanced glycation end products and enhanced oxidative stress, 
      leading to the progression of diabetic vascular disease. We have investigated the 
      mechanisms by which AGE-modified bovine albumin (AGE-BSA) induces reactive oxygen 
      species (ROS) generation, leading to nuclear factor-erythroid 2-related factor 
      (Nrf2) dependent induction of the antioxidant genes heme oxygenase-1 (HO-1) and 
      NADPH:quinone oxidoreductase 1 (NQO1) in bovine aortic endothelial cells. METHODS 
      AND RESULTS: AGE-BSA (100 mug ml(-)(1), 0-24 h), but not native BSA, elicited 
      time-dependent increases in ROS generation, Nrf2 nuclear translocation and 
      enhanced mRNA and protein expression of HO-1 and NQO1, but not glutathione 
      peroxidase-1. Inhibition of ROS production with the superoxide scavenger Tiron or 
      inhibitors of flavoproteins (diphenylene iodonium) and NADPH oxidase (apocynin), 
      but not eNOS (L-NAME) or mitochondria complex I (rotenone) abrogated HO-1 
      induction by AGE-BSA. Although AGE-BSA induced rapid phosphorylation of JNK and 
      Akt, only inhibition of JNK abrogated HO-1 expression, implicating the 
      involvement of the JNK signaling pathway in AGEs activation of Nrf2/ARE-linked 
      antioxidant gene expression. CONCLUSION: Our findings establish that AGEs 
      activate redox sensitive Nrf2-dependent antioxidant gene expression in bovine 
      aortic endothelial cells, providing an adaptive endogenous defense against 
      oxidative stress in diabetes.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - He, M
AU  - He M
AD  - Cardiovascular Division, School of Medicine, King's College London, 150 Stamford 
      Street, London SE1 9NH, UK.
FAU - Siow, R C M
AU  - Siow RC
FAU - Sugden, D
AU  - Sugden D
FAU - Gao, L
AU  - Gao L
FAU - Cheng, X
AU  - Cheng X
FAU - Mann, G E
AU  - Mann GE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100315
PL  - Netherlands
TA  - Nutr Metab Cardiovasc Dis
JT  - Nutrition, metabolism, and cardiovascular diseases : NMCD
JID - 9111474
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (advanced glycation end products-bovine serum albumin)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cells, Cultured
MH  - Diabetes Mellitus/physiopathology
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism
MH  - Enzyme Induction/drug effects
MH  - Free Radical Scavengers/pharmacology
MH  - Glycation End Products, Advanced/*toxicity
MH  - Heme Oxygenase-1/*biosynthesis/genetics
MH  - Hyperglycemia/physiopathology
MH  - NAD(P)H Dehydrogenase (Quinone)/genetics/metabolism
MH  - NF-E2-Related Factor 2/agonists/*metabolism
MH  - *Oxidative Stress
MH  - Protein Transport/drug effects
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Serum Albumin, Bovine/*toxicity
MH  - *Signal Transduction/drug effects
MH  - Time Factors
EDAT- 2010/03/17 06:00
MHDA- 2011/07/20 06:00
CRDT- 2010/03/16 06:00
PHST- 2009/09/16 00:00 [received]
PHST- 2009/12/08 00:00 [revised]
PHST- 2009/12/16 00:00 [accepted]
PHST- 2010/03/16 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2011/07/20 06:00 [medline]
AID - S0939-4753(09)00317-2 [pii]
AID - 10.1016/j.numecd.2009.12.008 [doi]
PST - ppublish
SO  - Nutr Metab Cardiovasc Dis. 2011 Apr;21(4):277-85. doi: 
      10.1016/j.numecd.2009.12.008. Epub 2010 Mar 15.