PMID- 23261472
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20131121
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 430
IP  - 4
DP  - 2013 Jan 25
TI  - Inactivation of GAPDH as one mechanism of acrolein toxicity.
PG  - 1265-71
LID - S0006-291X(12)02405-9 [pii]
LID - 10.1016/j.bbrc.2012.12.057 [doi]
AB  - We have recently reported that acrolein is more toxic than reactive oxygen 
      species. Thus, the mechanism of cell toxicity by acrolein was studied using mouse 
      mammary carcinoma FM3A cells. Acrolein-conjugated proteins were separated by gel 
      electrophoresis with subsequent determination of their amino acid sequence, and 
      it was found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was one of the 
      major acrolein-conjugated proteins in cells. Acrolein interacted with 
      cysteine-150 at the active site of GAPDH, and also with cysteine-282. When cells 
      were treated with 8 muM acrolein, the activity of acrolein-conjugated GAPDH was 
      greatly reduced, and the ATP content in cells was thus significantly reduced. In 
      addition, it was shown that acrolein-conjugated GAPDH translocated to the 
      nucleus, and the level of acetylated GAPDH and the number of TUNEL positive cells 
      was increased, indicating that cell death is enhanced by acrolein-conjugated 
      GAPDH. Inhibition of cell growth by acrolein was partially reversed when the cDNA 
      encoding GAPDH was transformed into cells. These results indicate that 
      inactivation of GAPDH is one mechanism that underlies cell toxicity caused by 
      acrolein.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Nakamura, Mizuho
AU  - Nakamura M
AD  - Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan.
FAU - Tomitori, Hideyuki
AU  - Tomitori H
FAU - Suzuki, Takehiro
AU  - Suzuki T
FAU - Sakamoto, Akihiko
AU  - Sakamoto A
FAU - Terui, Yusuke
AU  - Terui Y
FAU - Saiki, Ryotaro
AU  - Saiki R
FAU - Dohmae, Naoshi
AU  - Dohmae N
FAU - Igarashi, Kazuei
AU  - Igarashi K
FAU - Kashiwagi, Keiko
AU  - Kashiwagi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121220
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 7864XYD3JJ (Acrolein)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Acrolein/*metabolism/*toxicity
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cysteine/genetics/metabolism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/genetics/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Transformation, Genetic
EDAT- 2012/12/25 06:00
MHDA- 2013/08/07 06:00
CRDT- 2012/12/25 06:00
PHST- 2012/12/08 00:00 [received]
PHST- 2012/12/11 00:00 [accepted]
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
AID - S0006-291X(12)02405-9 [pii]
AID - 10.1016/j.bbrc.2012.12.057 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Jan 25;430(4):1265-71. doi: 
      10.1016/j.bbrc.2012.12.057. Epub 2012 Dec 20.