PMID- 22174393
OWN - NLM
STAT- MEDLINE
DCOM- 20120911
LR  - 20161125
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 112
IP  - 5
DP  - 2012 Mar
TI  - Nitric oxide modulates hypoxia-inducible factor-1 and poly(ADP-ribose) 
      polymerase-1 cross talk in response to hypobaric hypoxia.
PG  - 816-23
LID - 10.1152/japplphysiol.00898.2011 [doi]
AB  - The physiological response to hypobaric hypoxia represents a complex network of 
      biochemical pathways in which the nitrergic system plays an important role. 
      Previous studies have provided evidence for an interplay between the 
      hypoxia-inducible factor-1 (HIF-1) and poly(ADP-ribose) polymerase-1 (PARP-1) 
      under hypoxia. Here, we evaluate the potential involvement of nitric oxide (NO) 
      in the cross talk between these two proteins. With this aim, we studied 
      comparatively the effect of pharmacological inhibitors of NO production or PARP 
      activity in the response of the mouse cerebral cortex to 4 h of exposure to a 
      simulated altitude of 31,000 ft. Particularly, we analyzed the NO and reactive 
      oxygen species production, the expression of NO synthase (NOS) isoforms, PARP-1 
      activity, HIF-1alpha expression and HIF-1 transcriptional activity, the protein level 
      of the factor inhibiting HIF, and, finally, beclin-1 and fractin expression, as 
      markers of cellular damage. Our results demonstrate that the reduction of NO 
      level did not affect reactive oxygen species production but significantly 1) 
      dampened the posthypoxic increase in neuronal NOS and inducible NOS expression 
      without altering endothelial NOS protein level; 2) prevented PARP activation; 3) 
      decreased HIF-1alpha response to hypoxia; 4) achieved a higher long-term HIF-1 
      transcriptional activity by reducing factor inhibiting HIF expression; and 5) 
      reduced hypoxic damage. The pharmacological inhibition of PARP reproduced the NOS 
      expression pattern and the HIF-1alpha response observed in NOS-inhibited mice, 
      supporting its involvement in the NO-dependent regulation of hypoxia. As a whole, 
      these results provide new data about the molecular mechanism underlying the 
      beneficial effects of controlling NO production under hypobaric hypoxic 
      conditions.
FAU - Martinez-Romero, Ruben
AU  - Martinez-Romero R
AD  - Department of Experimental Biology, University of Jaen, Jaen, Spain.
FAU - Canuelo, Ana
AU  - Canuelo A
FAU - Siles, Eva
AU  - Siles E
FAU - Oliver, F Javier
AU  - Oliver FJ
FAU - Martinez-Lara, Esther
AU  - Martinez-Lara E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111215
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Altitude
MH  - Animals
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Beclin-1
MH  - Cerebral Cortex/drug effects/metabolism/physiopathology
MH  - Hypoxia/*metabolism/physiopathology
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/antagonists & inhibitors/*metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/*metabolism
MH  - Reactive Oxygen Species/metabolism
EDAT- 2011/12/17 06:00
MHDA- 2012/09/12 06:00
CRDT- 2011/12/17 06:00
PHST- 2011/12/17 06:00 [entrez]
PHST- 2011/12/17 06:00 [pubmed]
PHST- 2012/09/12 06:00 [medline]
AID - japplphysiol.00898.2011 [pii]
AID - 10.1152/japplphysiol.00898.2011 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2012 Mar;112(5):816-23. doi: 
      10.1152/japplphysiol.00898.2011. Epub 2011 Dec 15.