PMID- 18467643
OWN - NLM
STAT- MEDLINE
DCOM- 20080703
LR  - 20211020
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 28
IP  - 7
DP  - 2008 Jul
TI  - Nox4 and nox2 NADPH oxidases mediate distinct cellular redox signaling responses 
      to agonist stimulation.
PG  - 1347-54
LID - 10.1161/ATVBAHA.108.164277 [doi]
AB  - OBJECTIVE: The NADPH oxidase isoforms Nox2 and Nox4 are coexpressed in many cell 
      types and are implicated in agonist-stimulated redox-sensitive signal 
      transduction. We compared the involvement of Nox2 versus Nox4 in redox-sensitive 
      protein kinase activation after agonist stimulation. METHODS AND RESULTS: We 
      transfected HEK293 cells with Nox2 or Nox4 and compared ROS production and 
      activation of mitogen activated protein kinases (MAPKs), Akt, and GSK3beta after 
      acute agonist stimulation. Nox4 overexpression substantially increased basal ROS 
      generation whereas ROS generation in response to angiotensin II and tumor 
      necrosis factor (TNF)alpha was enhanced in Nox2-overexpressing cells. Nox4 
      overexpression induced basal activation of ERK1/2 and JNK whereas 
      Nox2-transfected cells showed a modest increase in p38MAPK activation. After 
      angiotensin II or TNFalpha treatment, JNK activation was augmented in Nox2 but 
      not Nox4-transfected cells, whereas insulin augmented phosphorylation of p38MAPK, 
      Akt, and GSK3beta specifically in Nox4-overexpressing cells and JNK specifically 
      in Nox2-overexpressing cells. CONCLUSIONS: These data indicate that Nox2 and Nox4 
      exhibit distinctive patterns of acute activation by angiotensin II, TNFalpha, and 
      insulin and regulate the activation of distinct protein kinases.
FAU - Anilkumar, Narayana
AU  - Anilkumar N
AD  - Department of Cardiology, The James Black Centre, King's College London, 125 
      Coldharbour Lane, London SE59NU, UK.
FAU - Weber, Roberta
AU  - Weber R
FAU - Zhang, Min
AU  - Zhang M
FAU - Brewer, Alison
AU  - Brewer A
FAU - Shah, Ajay M
AU  - Shah AM
LA  - eng
GR  - RG/08/011/25922/BHF_/British Heart Foundation/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080508
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Antibodies)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Insulin)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (catalase-polyethylene glycol)
RN  - 11128-99-7 (Angiotensin II)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (polyethylene glycol-superoxide dismutase)
RN  - EC 1.6.3.- (CYBB protein, human)
RN  - EC 1.6.3.- (Cybb protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (Nox4 protein, mouse)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Animals
MH  - Antibodies
MH  - COS Cells
MH  - Catalase/pharmacology
MH  - Chlorocebus aethiops
MH  - Endothelial Cells/drug effects/*enzymology
MH  - Enzyme Activation
MH  - Free Radical Scavengers/pharmacology
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Humans
MH  - Insulin/*metabolism
MH  - Membrane Glycoproteins/deficiency/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NADPH Oxidase 2
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/deficiency/genetics/immunology/*metabolism
MH  - Oxidation-Reduction
MH  - Phosphorylation
MH  - Polyethylene Glycols/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *Signal Transduction/drug effects
MH  - Superoxide Dismutase/pharmacology
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2008/05/10 09:00
MHDA- 2008/07/04 09:00
CRDT- 2008/05/10 09:00
PHST- 2008/05/10 09:00 [pubmed]
PHST- 2008/07/04 09:00 [medline]
PHST- 2008/05/10 09:00 [entrez]
AID - ATVBAHA.108.164277 [pii]
AID - 10.1161/ATVBAHA.108.164277 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1347-54. doi: 
      10.1161/ATVBAHA.108.164277. Epub 2008 May 8.