PMID- 16890367
OWN - NLM
STAT- MEDLINE
DCOM- 20070123
LR  - 20171116
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 142
IP  - 2
DP  - 2006 Oct 13
TI  - The induction of surface beta-amyloid binding proteins and enhanced cytotoxicity 
      in cultured PC-12 and IMR-32 cells by advanced glycation end products.
PG  - 463-73
AB  - During aging the non-enzymatic glycation of proteins and other molecules 
      increases significantly, leading to the accumulation of advanced glycation 
      end-products (AGEs). These AGEs enhance inflammatory and autoimmune reactions 
      with resultant cytotoxicity. We noted in an earlier study that individuals with 
      Alzheimer's disease exhibit enhanced expression of the receptor for advanced 
      glycation end-products (RAGE) on the surface of their leukocytes. In order to 
      better understand the relationship between AGEs and the cell surface binding of 
      amyloid-beta protein (Abeta) 42 we studied the effect of two AGEs: glycated 
      bovine serum albumin (BSA), and epsilon-carboxymethyllysine-BSA (CML), a 
      glycoxidation product, on the binding of Abeta42 to rat PC-12 and IMR-32 cells. 
      We measured the expression of three potential cell surface receptors binding 
      Abeta42: RAGE, beta-amyloid precursor protein (beta-APP), and the alpha7 subtype 
      of the nicotinic acetylcholine receptor (alpha7nAChR) by using specific antibody 
      probes. Incubation of PC-12 or IMR-32 cells with bovine serum albumin-advanced 
      glycation end-product (BSA-AGE) or with CML induced small but significant 
      concentration-dependent increases in the expression of beta-APP, RAGE, and 
      alpha7nAChRs as measured by flow cytometry or by ELISA. Incubation of the cells 
      with 48 microM of either of the AGEs combined with varying concentrations 
      (138-1100 nM) of Abeta42 resulted in the enhanced binding of the Abeta42 to the 
      cell surface as compared with cells not exposed to the AGE co-treatment. The 
      combination of AGE and Abeta treatment also resulted in the heightened expression 
      of all three potential Abeta binding sites as well as their gene precursors. 
      Exposure of cells to the same regimen of AGE plus Abeta resulted in the 
      production of reactive oxygen species and mitochondrial toxicity. These results 
      are consistent with the ability of AGEs to enhance the cell surface expression of 
      diverse Abeta42 binding sites, a factor that can lead to the enhanced binding of 
      amyloid and subsequent cell death.
FAU - Mruthinti, S
AU  - Mruthinti S
AD  - Alzheimer's Research Center, Department of Pharmacology and Toxicology, Medical 
      College of Georgia, 1120 15th Street, Augusta, GA 30912, USA. 
      shyamalamruthinti@yahoo.com
FAU - Sood, A
AU  - Sood A
FAU - Humphrey, C L
AU  - Humphrey CL
FAU - Swamy-Mruthinti, S
AU  - Swamy-Mruthinti S
FAU - Buccafusco, J J
AU  - Buccafusco JJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060804
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Chrna7 protein, human)
RN  - 0 (Chrna7 protein, rat)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Amyloid beta-Peptides/*pharmacology
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Flow Cytometry/methods
MH  - Gene Expression Regulation/*drug effects
MH  - Glycation End Products, Advanced/*metabolism/*pharmacology
MH  - Humans
MH  - Membrane Proteins/drug effects/*metabolism
MH  - Neuroblastoma
MH  - Peptide Fragments/*pharmacology
MH  - Protein Binding/drug effects
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Nicotinic/metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor
EDAT- 2006/08/08 09:00
MHDA- 2007/01/24 09:00
CRDT- 2006/08/08 09:00
PHST- 2005/10/24 00:00 [received]
PHST- 2006/06/08 00:00 [revised]
PHST- 2006/06/09 00:00 [accepted]
PHST- 2006/08/08 09:00 [pubmed]
PHST- 2007/01/24 09:00 [medline]
PHST- 2006/08/08 09:00 [entrez]
AID - S0306-4522(06)00807-4 [pii]
AID - 10.1016/j.neuroscience.2006.06.010 [doi]
PST - ppublish
SO  - Neuroscience. 2006 Oct 13;142(2):463-73. doi: 10.1016/j.neuroscience.2006.06.010. 
      Epub 2006 Aug 4.