PMID- 25677088
OWN - NLM
STAT- MEDLINE
DCOM- 20160609
LR  - 20210310
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 4
DP  - 2015
TI  - Rac1 modification by an electrophilic 15-deoxy Delta(12,14)-prostaglandin J2 analog.
PG  - 346-54
LID - S2213-2317(15)00018-X [pii]
LID - 10.1016/j.redox.2015.01.016 [doi]
AB  - Vascular endothelial cells (ECs) are important for maintaining vascular 
      homeostasis. Dysfunction of ECs contributes to cardiovascular diseases, including 
      atherosclerosis, and can impair the healing process during vascular injury. An 
      important mediator of EC response to stress is the GTPase Rac1. Rac1 responds to 
      extracellular signals and is involved in cytoskeletal rearrangement, reactive 
      oxygen species generation and cell cycle progression. Rac1 interacts with 
      effector proteins to elicit EC spreading and formation of cell-to-cell junctions. 
      Rac1 activity has recently been shown to be modulated by glutathiolation or 
      S-nitrosation via an active site cysteine residue. However, it is not known 
      whether other redox signaling compounds can modulate Rac1 activity. An important 
      redox signaling mediator is the electrophilic lipid, 
      15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2). This compound is a downstream 
      product of cyclooxygenase and forms covalent adducts with specific cysteine 
      residues, and induces cellular signaling in a pleiotropic manner. In this study, 
      we demonstrate that a biotin-tagged analog of 15d-PGJ2 (bt-15d-PGJ2) forms an 
      adduct with Rac1 in vitro at the C157 residue, and an additional adduct was 
      detected on the tryptic peptide associated with C178. Rac1 modification in 
      addition to modulation of Rac1 activity by bt-15d-PGJ2 was observed in cultured 
      ECs. In addition, decreased EC migration and cell spreading were observed in 
      response to the electrophile. These results demonstrate for the first time that 
      Rac1 is a target for 15d-PGJ2 in ECs, and suggest that Rac1 modification by 
      electrophiles such as 15d-PGJ2 may alter redox signaling and EC function.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Wall, S B
AU  - Wall SB
AD  - Center for Free Radical Biology and Department of Pathology, University of 
      Alabama at Birmingham, AL, USA.
FAU - Oh, J-Y
AU  - Oh JY
AD  - Center for Free Radical Biology and Department of Pathology, University of 
      Alabama at Birmingham, AL, USA.
FAU - Mitchell, L
AU  - Mitchell L
AD  - Department of Biochemistry and Biophysics, University of North Carolina, Chapel 
      Hill, NC, USA.
FAU - Laube, A H
AU  - Laube AH
AD  - Department of Biochemistry and Molecular Genetics, University of Alabama at 
      Birmingham, AL, USA.
FAU - Campbell, S L
AU  - Campbell SL
AD  - Department of Biochemistry and Biophysics, University of North Carolina, Chapel 
      Hill, NC, USA.
FAU - Renfrow, M B
AU  - Renfrow MB
AD  - Department of Biochemistry and Molecular Genetics, University of Alabama at 
      Birmingham, AL, USA.
FAU - Landar, A
AU  - Landar A
AD  - Center for Free Radical Biology and Department of Pathology, University of 
      Alabama at Birmingham, AL, USA. Electronic address: landar@uab.edu.
LA  - eng
GR  - T32 HL007918/HL/NHLBI NIH HHS/United States
GR  - P30 DK079337/DK/NIDDK NIH HHS/United States
GR  - T32 GM008111/GM/NIGMS NIH HHS/United States
GR  - T32HL007918/HL/NHLBI NIH HHS/United States
GR  - R01 CA089614/CA/NCI NIH HHS/United States
GR  - DK079337/DK/NIDDK NIH HHS/United States
GR  - R01CA08614/CA/NCI NIH HHS/United States
GR  - R01 HL096638/HL/NHLBI NIH HHS/United States
GR  - HL096638/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150203
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (15-deoxy-delta(12,14)-prostaglandin J2)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - 6SO6U10H04 (Biotin)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Animals
MH  - Aorta/cytology/metabolism
MH  - Biotin/chemistry
MH  - Cattle
MH  - Cell Movement
MH  - Endothelial Cells/cytology/*metabolism
MH  - Gene Expression
MH  - Peptide Fragments/analysis
MH  - Primary Cell Culture
MH  - Prostaglandin D2/*analogs & derivatives/chemistry/metabolism
MH  - *Protein Processing, Post-Translational
MH  - Proteolysis
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Signal Transduction
MH  - rac1 GTP-Binding Protein/chemistry/*metabolism
PMC - PMC4326178
OTO - NOTNLM
OT  - Cyclopentenone
OT  - Electrophile responsive proteome
OT  - Oxidative post-translational modification
OT  - Redox signaling
OT  - Rho GTPase
OT  - Thiol
EDAT- 2015/02/14 06:00
MHDA- 2016/06/10 06:00
PMCR- 2015/02/03
CRDT- 2015/02/14 06:00
PHST- 2014/12/23 00:00 [received]
PHST- 2015/01/29 00:00 [revised]
PHST- 2015/01/30 00:00 [accepted]
PHST- 2015/02/14 06:00 [entrez]
PHST- 2015/02/14 06:00 [pubmed]
PHST- 2016/06/10 06:00 [medline]
PHST- 2015/02/03 00:00 [pmc-release]
AID - S2213-2317(15)00018-X [pii]
AID - 10.1016/j.redox.2015.01.016 [doi]
PST - ppublish
SO  - Redox Biol. 2015;4:346-54. doi: 10.1016/j.redox.2015.01.016. Epub 2015 Feb 3.