Hypoxia-Inducible Factor Prolyl-Hydroxylase 2 Senses High-Salt Intake to Increase Hypoxia Inducible Factor 1&agr; Levels in the Renal Medulla

@article{Wang2010HypoxiaInducibleFP,
  title={Hypoxia-Inducible Factor Prolyl-Hydroxylase 2 Senses High-Salt Intake to Increase Hypoxia Inducible Factor 1\&agr; Levels in the Renal Medulla},
  author={Zheng-chao Wang and Qing Zhu and Min Xia and Pin-Lan Li and Shante J Hinton and Ningjun Li},
  journal={Hypertension},
  year={2010},
  volume={55},
  pages={1129-1136}
}
High salt induces the expression of transcription factor hypoxia-inducible factor (HIF) 1&agr; and its target genes in the renal medulla, which is an important renal adaptive mechanism to high-salt intake. HIF prolyl-hydroxylase domain-containing proteins (PHDs) have been identified as major enzymes to promote the degradation of HIF-1&agr;. PHD2 is the predominant isoform of PHDs in the kidney and is primarily expressed in the renal medulla. The present study tested the hypothesis that PHD2… Expand
Silencing of HIF prolyl-hydroxylase 2 gene in the renal medulla attenuates salt-sensitive hypertension in Dahl S rats.
TLDR
This study tested the hypothesis that silencing the PHD2 gene to increase HIF-1α levels in the renal medulla attenuates salt-sensitive hypertension in Dahl S rats and found it to be a therapeutic approach for salt- sensitive hypertension. Expand
Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
TLDR
It was shown that overexpression ofPHD2 transgene increased PHD2 levels and decreased HIF‐1α levels in the renal medulla, which blunted pressure natriuresis, attenuated sodium excretion, promoted sodium retention and produced salt sensitive hypertension after high salt challenge compared with rats treated with control plasmids. Expand
Regulation of hypoxia inducible factor/prolyl hydroxylase binding domain proteins 1 by PPARα and high salt diet
TLDR
The data suggest that HS-induced PPARα-mediated downregulation of PHD1 is a novel pathway for PHD/HIF-1α transcriptional regulation for adaptive responses to promote renal function via downstream signaling involving NOS and HO. Expand
Hypoxia inducible factor-1α-mediated gene activation in the regulation of renal medullary function and salt sensitivity of blood pressure.
  • Ningjun Li
  • Medicine
  • American journal of cardiovascular disease
  • 2012
Many enzymes that produce natriuretic factors such as nitric oxide synthase (NOS), hemeoxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) are highly expressed in the renal medulla. These enzymes in theExpand
Inhibition of microRNA-429 in the renal medulla increased salt sensitivity of blood pressure in Sprague Dawley rats
TLDR
It is concluded that miR-429 is an important upstream mediator in PHD2/HIF-1&agr;-associated renal adaptation to high salt intake and that deficiency in miR -429-mediatedPHD2 inhibition in response to high Salt in the renal medulla may represent a pathogenic mechanism for salt-sensitive hypertension. Expand
Overexpression of HIF-1α transgene in the renal medulla attenuated salt sensitive hypertension in Dahl S rats.
TLDR
It is suggested that an abnormal Hif-1α in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1 α levels in the kidney medulla could be a therapeutic approach for the treatment of salt- sensitive hypertension. Expand
Inhibition of prolyl hydroxylase domain-containing protein on hypertension/renal injury induced by high salt diet and nitric oxide withdrawal
TLDR
Exacerbation of hypertension and renal injury following PHD inhibition suggests a deleterious effect in the chronic setting and challenges the dogma that inhibition of PHD is useful in cardiovascular diseases. Expand
The Role of Hypoxia-Inducible Factor/Prolyl Hydroxylation Pathway in Deoxycorticosterone Acetate/Salt Hypertension in the Rat.
TLDR
The data suggest that reduced PHD2 expression with consequent increase in HIF-1α expression probably results from hypoxia induced by DOCA/salt treatment with the continued Hypoxia and reduced PHd2 expression evoking hypertensive renal injury and collagen deposition at later stages. Expand
Silencing of hypoxia-inducible factor-1α gene attenuates chronic ischemic renal injury in two-kidney, one-clip rats.
TLDR
Long-term overactivation of HIF-1α is a pathogenic factor in chronic renal injury associated with ischemia/hypoxia and this effect was blocked by shRNA. Expand
Overexpression of hypoxia-inducible factor prolyl hydoxylase-2 attenuates hypoxia-induced vascular endothelial growth factor expression in luteal cells.
TLDR
The results of the present study indicated that PHD2 is the main PHD expressed in LCs and hypoxia‑induced VEGF expression can be attenuated byPHD2 overexpression through HIF‑1α‑mediated mechanisms inLCs. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 72 REFERENCES
Salt-Sensitive Hypertension Induced by Decoy of Transcription Factor Hypoxia-Inducible Factor-1&agr; in the Renal Medulla
TLDR
Test the hypothesis that HIF-1&agr;–mediated gene activation serves as an antihypertensive pathway by regulating renal medullary function and sodium excretion in decoy rats and found it importantly participates in the regulation of renal medulla function and long-term arterial blood pressure. Expand
Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys.
TLDR
Results indicate that highly expressed PHDs in the renal medulla make an important contribution to the control of renal Na(+) excretion through regulation of HIF-1alpha and its targeted genes. Expand
Salt-Sensitive Hypertension Induced by Decoy of Transcription Factor Hypoxia-Inducible Factor-1α in the Renal Medulla
TLDR
Test the hypothesis that HIF-1α–mediated gene activation serves as an antihypertensive pathway by regulating renal medullary function and sodium excretion by transfecting Sprague–Dawley rats with decoy ODNs to test this hypothesis. Expand
HIF-prolyl hydroxylases in the rat kidney: physiologic expression patterns and regulation in acute kidney injury.
TLDR
The results implicate the non-uniform expression of HIF-regulating enzymes that modify the hypoxic response in the kidney under both regional and temporal conditions. Expand
OS-9 Interacts with Hypoxia-Inducible Factor 1α and Prolyl Hydroxylases to Promote Oxygen-Dependent Degradation of HIF-1α
TLDR
OS-9 is an essential component of a multiprotein complex that regulates HIF-1alpha levels in an O2-dependent manner, and its gain-of-function promotes Hif-1 alpha hydroxylation, VHL binding, proteasomal degradation of HIF -1alpha, and inhibition of H IF-1-mediated transcription. Expand
Hypoxia-inducible factor-1alpha stabilization in nonhypoxic conditions: role of oxidation and intracellular ascorbate depletion.
TLDR
It is shown that HIF-1alpha stability is mediated through the Ang II-mediated generation of hydrogen peroxide and a subsequent decrease in ascorbate levels, leading to decreased HIF prolyl-hydroxylase activity and Hif-1 alpha stabilization. Expand
Hypoxia Up-regulates Prolyl Hydroxylase Activity
TLDR
The results suggest that a hypoxic upregulation of PHD (presumably PHD-2) acts as a feedback mechanism to stop hypoxic responses in reoxygenated cells and it is proposed that proline hydroxylation might play a role in hypoxic preconditioning. Expand
Nitric oxide reverses desferrioxamine- and hypoxia-evoked HIF-1alpha accumulation--implications for prolyl hydroxylase activity and iron.
TLDR
Variables that allow efficient PHD activation such as oxygen availability, iron content, or cofactor accessibility at that end allow NO to modulate HIF-1alpha accumulation, and it is assumed that increased intracellular free iron contributes to regain PHD activity. Expand
Sequence Determinants in Hypoxia-inducible Factor-1α for Hydroxylation by the Prolyl Hydroxylases PHD1, PHD2, and PHD3*
TLDR
It is reported here that PHD2 has the highest specific activity toward the primary hydroxylation site of HIF-1α, and unexpectedly, mutations can be tolerated at the −5, −2, and −1 positions (relative to proline) of the LXXLAP motif. Expand
Non-hypoxic activation of the negative regulatory feedback loop of prolyl-hydroxylase oxygen sensors.
TLDR
Induction of endogenous PHD2 activity by NO is dependent on a feedback loop initiated despite normoxic conditions and was not found in cells that lack an intact pVHL dependent degradation pathway. Expand
...
1
2
3
4
5
...