PMID- 14616239
OWN - NLM
STAT- MEDLINE
DCOM- 20040202
LR  - 20171116
IS  - 0001-6772 (Print)
IS  - 0001-6772 (Linking)
VI  - 179
IP  - 3
DP  - 2003 Nov
TI  - Reactive oxygen species and molecular regulation of renal oxygenation.
PG  - 233-41
AB  - It has been known since the 1940s that a gradient of renal oxygenation exists in 
      the kidney with the lowest PO2 in the renal inner medulla under physiological 
      conditions. Due to a low PO2 milieu in the renal medulla, the cells in this 
      region are at constant risk of hypoxic injury. Although numerous studies have 
      shown that renal medullary cells adapt well to low PO2, the precise mechanism 
      mediating this adaptive response remains poorly understood. Recently, 
      hypoxia-induced molecular adaptation in mammalian tissues or cells has been 
      studied extensively and many studies have indicated that the molecular regulation 
      of gene expression is importantly involved. This paper focuses on the role of a 
      transcription factor, hypoxia-inducible factor-1 (HIF-1)-mediated molecular 
      adaptation and explores the physiological relevance of molecular activation of 
      HIF-1 and its target genes in the renal medulla. Given that this HIF-1-mediated 
      action is associated with local redox status, evidence is presented to indicate 
      that reactive oxygen species (ROS), especially superoxide (O) is importantly 
      involved in HIF-1-mediated molecular adaptation in renal medullary cells. O 
      degrades HIF-1alpha, an HIF-1 subunit, by activating ubiquitin-proteasome and 
      thereby decreases the transcriptional activation of many oxygen-sensitive genes. 
      This action of O disturbs renal medullary adaptation to low PO2 and produces 
      renal medullary dysfunction, resulting in sodium retention and hypertension. This 
      report also provides evidence indicating the primary source of O, enzymatic 
      pathways for O production and activating mechanism of O production in the kidney. 
      It is concluded that HIF-1-mediated molecular adaptation to low PO2 is of 
      importance in the regulation of renal medullary function and that ROS may target 
      this HIF-1-mediated medullary adaptation to damage renal function.
FAU - Zou, A-P
AU  - Zou AP
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Cowley, A W Jr
AU  - Cowley AW Jr
LA  - eng
GR  - DK-54927/DK/NIDDK NIH HHS/United States
GR  - HL29587/HL/NHLBI NIH HHS/United States
GR  - HL70726/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Acta Physiol Scand
JT  - Acta physiologica Scandinavica
JID - 0370362
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factors)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kidney/metabolism/*physiology
MH  - Kidney Medulla/physiology
MH  - Loop of Henle/metabolism
MH  - NADPH Oxidases/metabolism
MH  - Oxidation-Reduction
MH  - Oxygen/physiology
MH  - Reactive Oxygen Species/*metabolism
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic/*genetics
RF  - 68
EDAT- 2003/11/18 05:00
MHDA- 2004/02/03 05:00
CRDT- 2003/11/18 05:00
PHST- 2003/11/18 05:00 [pubmed]
PHST- 2004/02/03 05:00 [medline]
PHST- 2003/11/18 05:00 [entrez]
AID - 1206 [pii]
AID - 10.1046/j.0001-6772.2003.01206.x [doi]
PST - ppublish
SO  - Acta Physiol Scand. 2003 Nov;179(3):233-41. doi: 
      10.1046/j.0001-6772.2003.01206.x.