PMID- 17442735
OWN - NLM
STAT- MEDLINE
DCOM- 20070920
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 293
IP  - 2
DP  - 2007 Aug
TI  - MKP-1 switches arginine metabolism from nitric oxide synthase to arginase 
      following endotoxin challenge.
PG  - C632-40
AB  - L-Arginine (L-arg) is metabolized to nitric oxide (NO) by inducible NO synthase 
      (iNOS) or to urea and L-ornithine (L-orn) by arginase. NO is involved in the 
      inflammatory response, whereas arginase is the first step in polyamine and 
      proline synthesis necessary for tissue repair and wound healing. 
      Mitogen-activated protein kinases (MAPK) mediate LPS-induced iNOS expression, and 
      MAPK phosphatase-1 (MKP-1) plays a crucial role in limiting MAPK signaling in 
      macrophages. We hypothesized that MKP-1, by attenuating iNOS expression, acts as 
      a switch changing L-arg metabolism from NO production to L-orn production after 
      endotoxin administration. To test this hypothesis, we performed studies in 
      RAW264.7 macrophages stably transfected with an MKP-1 expression vector in 
      thioglyollate-elicited peritoneal macrophages harvested from wild-type and 
      Mkp-1(-/-) mice, as well as in vivo in wild-type and Mkp-1(-/-) mice. We found 
      that overexpression of MKP-1 resulted in lower iNOS expression and NO production 
      but greater urea production in response to LPS. Although deficiency of MKP-1 
      resulted in greater iNOS expression and NO production and lower urea production 
      in response to LPS, neither the overexpression nor the deficiency of MKP-1 had 
      any substantial effect on the expression of the arginases.
FAU - Nelin, Leif D
AU  - Nelin LD
AD  - Center for Perinatal Research, Columbus Children's Research Institute, Columbus, 
      OH 43205, USA. NelinL@pediatrics.ohio-state.edu
FAU - Wang, Xianxi
AU  - Wang X
FAU - Zhao, Qun
AU  - Zhao Q
FAU - Chicoine, Louis G
AU  - Chicoine LG
FAU - Young, Tamara L
AU  - Young TL
FAU - Hatch, Dionna M
AU  - Hatch DM
FAU - English, B Keith
AU  - English BK
FAU - Liu, Yusen
AU  - Liu Y
LA  - eng
GR  - AI057798-01/AI/NIAID NIH HHS/United States
GR  - HL04050/HL/NHLBI NIH HHS/United States
GR  - HL075261/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070418
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (lipopolysaccharide, E coli O55-B5)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8W8T17847W (Urea)
RN  - 94ZLA3W45F (Arginine)
RN  - E524N2IXA3 (Ornithine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Dusp1 protein, mouse)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.5.3.1 (Arg2 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Animals
MH  - Arginase/genetics/*metabolism
MH  - Arginine/*metabolism
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Dual Specificity Phosphatase 1
MH  - Gene Expression Regulation, Enzymologic
MH  - Immediate-Early Proteins/deficiency/genetics/*metabolism
MH  - Inflammation/enzymology/genetics/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophages, Peritoneal/*drug effects/enzymology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type II/genetics/*metabolism
MH  - Ornithine/metabolism
MH  - Phosphoprotein Phosphatases/deficiency/genetics/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Phosphatase 1
MH  - Protein Tyrosine Phosphatases/deficiency/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Time Factors
MH  - Transfection
MH  - Urea/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
EDAT- 2007/04/20 09:00
MHDA- 2007/09/21 09:00
CRDT- 2007/04/20 09:00
PHST- 2007/04/20 09:00 [pubmed]
PHST- 2007/09/21 09:00 [medline]
PHST- 2007/04/20 09:00 [entrez]
AID - 00137.2006 [pii]
AID - 10.1152/ajpcell.00137.2006 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2007 Aug;293(2):C632-40. doi: 
      10.1152/ajpcell.00137.2006. Epub 2007 Apr 18.