scholarly journals PARP Inhibitor Protects Against Chronic Hypoxia/Reoxygenation-Induced Retinal Injury by Regulation of MAPKs, HIF1α, Nrf2, and NFκB

2019 ◽  
Vol 60 (5) ◽  
pp. 1478 ◽  
Author(s):  
Krisztina Kovacs ◽  
Alexandra Vaczy ◽  
Katalin Fekete ◽  
Petra Kovari ◽  
Tamas Atlasz ◽  
...  
Keyword(s):  
Chronic Hypoxia ◽  
Parp Inhibitor ◽  
Retinal Injury ◽  
Hypoxia Reoxygenation

scholarly journals Nrf2-AKT interactions regulate heme oxygenase 1 expression in kidney epithelia during hypoxia and hypoxia-reoxygenation

2016 ◽  
Vol 311 (5) ◽  
pp. F1025-F1034 ◽  
Author(s):  
Haranatha R. Potteti ◽  
Chandramohan R. Tamatam ◽  
Rakesh Marreddy ◽  
Narsa M. Reddy ◽  
Sanjeev Noel ◽  
...  
Keyword(s):  
Chronic Hypoxia ◽  
Ischemia Reperfusion ◽  
Acute Hypoxia ◽  
Kidney Injury ◽  
Clinical Problem ◽  
Proximal Promoter ◽  
Heme Oxygenase 1 ◽  
Antioxidant Genes ◽  
Underlying Mechanisms ◽  
Hypoxia Reoxygenation

Ischemia-reperfusion (IR)-induced kidney injury is a major clinical problem, but its underlying mechanisms remain unclear. The transcription factor known as nuclear factor, erythroid 2-like 2 (NFE2L2 or Nrf2) is crucial for protection against oxidative stress generated by pro-oxidant insults. We have previously shown that Nrf2 deficiency enhances susceptibility to IR-induced kidney injury in mice and that its upregulation is protective. Here, we examined Nrf2 target antioxidant gene expression and the mechanisms of its activation in both human and murine kidney epithelia following acute (2 h) and chronic (12 h) hypoxia and reoxygenation conditions. We found that acute hypoxia modestly stimulates and chronic hypoxia strongly stimulates Nrf2 putative target HMOX1 expression, but not that of other antioxidant genes. Inhibition of AKT1/2 or ERK1/2 signaling blocked this induction; AKT1/2 but not ERK1/2 inhibition affected Nrf2 levels in basal and acute hypoxia-reoxygenation states. Unexpectedly, chromatin immunoprecipitation assays revealed reduced levels of Nrf2 binding at the distal AB1 and SX2 enhancers and proximal promoter of HMOX1 in acute hypoxia, accompanied by diminished levels of nuclear Nrf2. In contrast, Nrf2 binding at the AB1 and SX2 enhancers significantly but differentially increased during chronic hypoxia and reoxygenation, with reaccumulation of nuclear Nrf2 levels. Small interfering-RNA-mediated Nrf2 depletion attenuated acute and chronic hypoxia-inducible HMOX1 expression, and primary Nrf2-null kidney epithelia showed reduced levels of HMOX1 induction in response to both acute and chronic hypoxia. Collectively, our data demonstrate that Nrf2 upregulates HMOX1 expression in kidney epithelia through a distinct mechanism during acute and chronic hypoxia reoxygenation, and that both AKT1/2 and ERK1/2 signaling are required for this process.

scholarly journals Dehydroepiandrosterone reverses chronic hypoxia/reoxygenation-induced right ventricular dysfunction in rats

2012 ◽  
Vol 40 (6) ◽  
pp. 1420-1429 ◽  
Author(s):  
Eric Dumas de La Roque ◽  
Nadège Bellance ◽  
Rodrigue Rossignol ◽  
Hugues Begueret ◽  
Marie Billaud ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Chronic Hypoxia ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Hypoxia Reoxygenation

Hypoxia/Reoxygenation on human myometrial and decidual cells: A molecular mechanism involved in preterra labor

1998 ◽  
Vol 5 (1) ◽  
pp. 187A-187A
Author(s):  
J CARVAJAL ◽  
S KATO ◽  
J SAEZ ◽  
F LEIGHTON ◽  
G VALENZUELA ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Decidual Cells ◽  
Hypoxia Reoxygenation

PARP inhibitor pick-me-up

2019 ◽  
Vol 18 (11) ◽  
pp. 814-814 ◽  
Author(s):  
Asher Mullard
Keyword(s):  
Parp Inhibitor

Neu diagnostiziertes Ovarialkarzinom

2019 ◽  
Vol 10 (03) ◽  
pp. 113-113
Author(s):  
Susanne Krome
Keyword(s):  
Parp Inhibitor

Nach einer zytoreduktiven Operation und Chemotherapie erleiden 70 % der Patientinnen mit Ovarialkarzinomen innerhalb von 3 Jahren ein Rezidiv. Der PARP-Inhibitor Olaparib war bei Frauen mit BRCA1/2-Mutation und platinsensitiven Rückfällen eine effektive Erhaltungstherapie. Die SOLO1-Studie belegt die Wirksamkeit von Olaparib nun auch bei neu diagnostizierten Karzinomen.

Preclinical evaluation of the PARP-inhibitor olaparib for the treatment of ovarian clear cell cancer

2011 ◽  
Vol 71 (08) ◽  
Author(s):  
KJ Dedes ◽  
P Wilkerson ◽  
D Wetterskog ◽  
MB Lambros ◽  
R Natrajan ◽  
...  
Keyword(s):  
Clear Cell ◽  
Parp Inhibitor ◽  
Cell Cancer ◽  
Preclinical Evaluation
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