scholarly journals Synthesis and evaluation of novel 12-aryl berberine analogues with hypoxia-inducible factor-1 inhibitory activity

RSC Advances ◽  
2017 ◽  
Vol 7 (43) ◽  
pp. 26921-26929 ◽  
Author(s):  
Xiaobo Zhou ◽  
Ming Chen ◽  
Zhiyuan Zheng ◽  
Guo-Yuan Zhu ◽  
Zhi-Hong Jiang ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Transcriptional Activity ◽  
Hypoxia Inducible Factor ◽  
Inhibitory Effect ◽  
Hypoxia Inducible Factor 1 ◽  
Potent Inhibitory Effect

Seven novel 12-phenyl berberines (3a–3f, 3k) showed more potent inhibitory effect on hypoxia-induced HIF-1 transcriptional activity than the parent berberine.

Nitric oxide modulates hypoxia-inducible factor-1 and poly(ADP-ribose) polymerase-1 cross talk in response to hypobaric hypoxia

2012 ◽  
Vol 112 (5) ◽  
pp. 816-823 ◽  
Author(s):  
Rubén Martínez-Romero ◽  
Ana Cañuelo ◽  
Eva Siles ◽  
F. Javier Oliver ◽  
Esther Martínez-Lara
Keyword(s):  
Nitric Oxide ◽  
Hypobaric Hypoxia ◽  
Reactive Oxygen Species Production ◽  
Transcriptional Activity ◽  
Hypoxia Inducible Factor ◽  
No Production ◽  
Oxygen Species ◽  
Hypoxia Inducible Factor 1 ◽  
Species Production ◽  
Parp 1

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-1α 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-1α 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-1α 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.

scholarly journals Virus-based reporter systems for monitoring transcriptional activity of hypoxia-inducible factor 1

Gene ◽  
2005 ◽  
Vol 350 (1) ◽  
pp. 89-98 ◽  
Author(s):  
O.V. Razorenova ◽  
A.V. Ivanov ◽  
A.V. Budanov ◽  
P.M. Chumakov
Keyword(s):  
Transcriptional Activity ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Reporter Systems

ChemInform Abstract: Diaryl-Substituted Carboranes as Inhibitors of Hypoxia Inducible Factor-1 Transcriptional Activity

ChemInform ◽  
2015 ◽  
Vol 46 (24) ◽  
pp. no-no
Author(s):  
Hiroyuki Nakamura ◽  
Lisa Tazaki ◽  
Daisuke Kanoh ◽  
Shinichi Sato
Keyword(s):  
Transcriptional Activity ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors

2021 ◽  
Vol 22 (22) ◽  
pp. 12335
Author(s):  
Yaozhong Hu ◽  
Ema Romão ◽  
Cécile Vincke ◽  
Lea Brys ◽  
Yvon Elkrim ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Condition ◽  
Inhibitory Effect ◽  
Intracellular Expression ◽  
Proliferation And Metastasis ◽  
Immune Library ◽  
Selection Of

Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1.

scholarly journals HIF-1: the knowns and unknowns of hypoxia sensing.

2004 ◽  
Vol 51 (3) ◽  
pp. 563-585 ◽  
Author(s):  
Anna Zagórska ◽  
Józef Dulak
Keyword(s):  
Transcriptional Activity ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Hypoxic Conditions ◽  
Oxygen Homeostasis ◽  
Wide Range ◽  
Systemic Oxygen ◽  
Prolyl Hydroxylation ◽  
Energy Deprivation ◽  
Direct Inhibitors

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that functions as a master regulator of cellular and systemic oxygen homeostasis. It consists of two constitutively produced subunits: HIF-1alpha and HIF-1beta. Under normoxic conditions HIF-1alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the alpha subunit. Additionally, hydroxylation of an asparaginyl residue blocks the transcriptional activity of HIF-1 due to inhibition of its interaction with co-activators. In contrast, under hypoxic conditions, abolition of prolyl hydroxylation results in HIF-1alpha stabilization, whereas the lack of asparaginyl hydroxylation allows the transcriptional activity. Additionally, the transcriptional activity may be modulated by phosphorylation or redox modification of HIF-1. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, various growth factors, or direct inhibitors of prolyl and asparaginyl hydroxylases. Therefore, it seems to be a crucial transcription factor elicited by a wide range of stresses such as impaired oxygenation, inflammation, energy deprivation, or intensive proliferation. However, the mechanisms of normoxic activation, as well as of oxygen sensing, are not yet fully known. Further understanding of the processes that control HIF-1 activity will be crucial for the development of new diagnostic and therapeutic strategies.

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