PMID- 8928897
OWN - NLM
STAT- MEDLINE
DCOM- 19961127
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 270
IP  - 5 Pt 2
DP  - 1996 May
TI  - NF-kappa B and GTP cyclohydrolase regulate cytokine-induced nitric oxide 
      production by cardiac myocytes.
PG  - H1864-8
AB  - We previously reported that interleukin-1 beta (IL-1) alone stimulated nitric 
      oxide (NO) production by neonatal rat cardiac myocytes (CM) in culture. The 
      present studies were undertaken to explore the signal transduction pathways 
      involved in IL-1-induced NO production by CM. Translocation from the cytosol to 
      the nucleus of nuclear factor-kappa B (NF-kappa B) and activation of guanosine 
      5'-triphosphate (GTP) cyclohydrolase [rate-limiting enzyme in tetrahydrobiopterin 
      (BH4) synthesis] have been implicated in IL-1 signaling. Accordingly, the effects 
      of the NF-kappa B inhibitor pyrolidine dithiocarbamate (PDTC) and the GTP 
      cyclohydrolase inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP) on IL-1-induced 
      NO production by CM were studied. PDTC and DAHP inhibited IL-1-induced 
      NO2-production by CM (6.7 +/- 0.6 vs. 0.9 +/- 0.3 and 0.3 +/- 0.1 nmol. 1.25 x 
      10(5) cells(-1).48 h-1, respectively, P < 0.01, n = 12 for each). 
      Immunohistochemical staining revealed that PDTC blocked IL-1-stimulated nuclear 
      translocation of NF-kappa B. The membrane-permeable analogue of the NO synthase 
      cofactor BH4, methyl-BH4 (mBH4), only partially reversed DAHP inhibition of NO2- 
      formation (6.7 +/- 0.6 vs. 2.4 +/- 0.3 nmol. 1.25 x 10(5) cells-1.48 h-1, P < 
      0.01, n = 12). Semiquantitative reverse transcription polymerase chain reaction 
      revealed no inducible NO synthase (iNOS) mRNA production in cells treated with 
      IL-1 + PDTC.CM treated with IL-1 + DAHP did express iNOS mRNA. We report for the 
      first time that nuclear translocation of NF-kappa B is essential for II-1-induced 
      iNOS mRNA expression and GTP cyclohydrolase activity is required in addition in 
      addition to BH4 for optimal NO production by CM.
FAU - Oddis, C V
AU  - Oddis CV
AD  - Department of Pathology, University of Pittsburgh, Pennsylvania 15213, USA.
FAU - Finkel, M S
AU  - Finkel MS
LA  - eng
GR  - GM-37753/GM/NIGMS NIH HHS/United States
GR  - HL-53372/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Pterins)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - C9AO82G1R1 (6-methyltetrahydropterin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Enzyme Induction
MH  - GTP Cyclohydrolase/*physiology
MH  - Interleukin-1/*pharmacology
MH  - Myocardium/cytology/*metabolism
MH  - NF-kappa B/*physiology
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/genetics
MH  - Pterins/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - 10.1152/ajpheart.1996.270.5.H1864 [doi]
PST - ppublish
SO  - Am J Physiol. 1996 May;270(5 Pt 2):H1864-8. doi: 
      10.1152/ajpheart.1996.270.5.H1864.