PMID- 10535332
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190719
IS  - 0361-9230 (Print)
IS  - 0361-9230 (Linking)
VI  - 50
IP  - 2
DP  - 1999 Sep 15
TI  - Methionine residue 35 is important in amyloid beta-peptide-associated free
      radical oxidative stress.
PG  - 133-41
AB  - Amyloid beta-peptide (Abeta), the central constituent of senile plaques in
      Alzheimer's disease (AD) brain, has been shown to be a source of free radical
      oxidative stress that may lead to neurodegeneration. In the current study
      Abeta(1-40), found in AD brain, and the amyloid fragment Abeta(25-35) were used
      in conjunction with electron paramagnetic resonance spin trapping techniques to
      demonstrate that these peptides mediate free radical production. The methionine
      residue in these peptides is believed to play an important role in their
      neurotoxicity. Substitution of methionine by structurally similar norleucine in
      both Abeta(1-40) and Abeta(25-35), and the substitution of methionine by valine, 
      or the removal of the methionine in Abeta(25-35), abrogates free radical
      production and protein oxidation of and toxicity to hippocampal neurons. These
      results are discussed with relevance to the hypothesis that neurodegeneration in 
      Alzheimer's disease may be due in part to Abeta-associated free radical oxidative
      stress that involves methionine, and to the use of spin trapping methods to infer
      mechanistic information about Abeta.
FAU - Varadarajan, S
AU  - Varadarajan S
AD  - Department of Chemistry, Center of Membrane Sciences, University of Kentucky,
      Lexington 40506-0055, USA.
FAU - Yatin, S
AU  - Yatin S
FAU - Kanski, J
AU  - Kanski J
FAU - Jahanshahi, F
AU  - Jahanshahi F
FAU - Butterfield, D A
AU  - Butterfield DA
LA  - eng
GR  - AG-05119/AG/NIA NIH HHS/United States
GR  - AG-10836/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Free Radicals)
RN  - 0 (Neurotoxins)
RN  - 0 (Tetrazolium Salts)
RN  - AE28F7PNPL (Methionine)
RN  - I2ZWO3LS3M (Trypan Blue)
SB  - IM
MH  - Alzheimer Disease/*physiopathology
MH  - Amyloid beta-Peptides/chemistry/*physiology/*toxicity
MH  - Animals
MH  - Cells, Cultured
MH  - Fetus/cytology
MH  - Free Radicals/adverse effects/pharmacology
MH  - Methionine/*metabolism/*toxicity
MH  - Neurons/cytology/drug effects
MH  - Neurotoxins/pharmacology
MH  - Oxidative Stress/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spin Trapping/methods
MH  - Tetrazolium Salts
MH  - Trypan Blue
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - S0361-9230(99)00093-3 [pii]
AID - 10.1016/s0361-9230(99)00093-3 [doi]
PST - ppublish
SO  - Brain Res Bull. 1999 Sep 15;50(2):133-41. doi: 10.1016/s0361-9230(99)00093-3.