PMID- 18459142
OWN - NLM
STAT- MEDLINE
DCOM- 20081015
LR  - 20151119
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 104
IP  - 6
DP  - 2008 Aug 15
TI  - PARP-1 modulates deferoxamine-induced HIF-1alpha accumulation through the 
      regulation of nitric oxide and oxidative stress.
PG  - 2248-60
LID - 10.1002/jcb.21781 [doi]
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that, once activated 
      by genotoxic agents, modulates the activity of several nuclear proteins including 
      itself. Previous studies have established that PARP-1 inhibition may provide 
      benefit in the treatment of different diseases, particularly those involving a 
      hypoxic situation, in which an increased oxidative and nitrosative stress occurs. 
      One of the most important transcription factors involved in the response to the 
      hypoxic situation is the hypoxia-inducible factor-1 (HIF-1). The activity of 
      HIF-1 is determined by the accumulation of its alpha subunit which is regulated, 
      in part, by oxidative stress (ROS) and nitric oxide (NO), both of them highly 
      dependent on PARP-1. Besides, HIF-1alpha can be induced by iron chelators such as 
      deferoxamine (DFO). In this sense, the therapeutical use of DFO to strengthen the 
      post-hypoxic response has recently been proposed. Taking into account the 
      increasing interest and potential clinical applications of PARP inhibition and 
      DFO treatment, we have evaluated the impact of PARP-1 on HIF-1alpha accumulation 
      induced by treatment with DFO. Our results show that, in DFO treated cells, 
      PARP-1 gene deletion or inhibition decreases HIF-1alpha accumulation. This lower 
      HIF-1alpha stabilization is parallel to a decreased inducible NO synthase 
      induction and NO production, a higher response of some antioxidant enzymes 
      (particularly glutathione peroxidase and glutathione reductase) and a lower ROS 
      level. Taken together, these results suggest that the absence of PARP-1 modulates 
      HIF-1 accumulation by reducing both NO and oxidative stress.
FAU - Martinez-Romero, Ruben
AU  - Martinez-Romero R
AD  - Department of Experimental Biology, University of Jaen, Paraje Las Lagunillas 
      s/n, 23071-Jaen, Spain.
FAU - Martinez-Lara, Esther
AU  - Martinez-Lara E
FAU - Aguilar-Quesada, Rocio
AU  - Aguilar-Quesada R
FAU - Peralta, Andreina
AU  - Peralta A
FAU - Oliver, F Javier
AU  - Oliver FJ
FAU - Siles, Eva
AU  - Siles E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Antioxidants)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 148498-78-6 (Adrenomedullin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Adrenomedullin/genetics/metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Blotting, Western
MH  - Deferoxamine/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Mice
MH  - Microscopy, Confocal
MH  - Models, Biological
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/deficiency/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - Thermodynamics
MH  - Time Factors
EDAT- 2008/05/07 09:00
MHDA- 2008/10/16 09:00
CRDT- 2008/05/07 09:00
PHST- 2008/05/07 09:00 [pubmed]
PHST- 2008/10/16 09:00 [medline]
PHST- 2008/05/07 09:00 [entrez]
AID - 10.1002/jcb.21781 [doi]
PST - ppublish
SO  - J Cell Biochem. 2008 Aug 15;104(6):2248-60. doi: 10.1002/jcb.21781.