Hypoxia Inducible Factor-1: Its Potential Role In Cerebral Ischemia

2012 ◽  
Vol 32 (4) ◽  
pp. 491-507 ◽  
Author(s):  
Neetu Singh ◽  
Gaurav Sharma ◽  
Vikas Mishra ◽  
Ram Raghubir
Keyword(s):  
Cerebral Ischemia ◽  
Potential Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Bartonella Adhesin A Mediates a Proangiogenic Host Cell Response

2004 ◽  
Vol 200 (10) ◽  
pp. 1267-1278 ◽  
Author(s):  
Tanja Riess ◽  
Siv G.E. Andersson ◽  
Andrei Lupas ◽  
Martin Schaller ◽  
Andrea Schäfer ◽  
...  
Keyword(s):  
Potential Role ◽  
Bartonella Henselae ◽  
Hypoxia Inducible Factor ◽  
Host Cells ◽  
Matrix Proteins ◽  
Vascular Endothelial ◽  
Host Cell Response ◽  
Hypoxia Inducible Factor 1 ◽  
In Trans ◽  
Endothelial Growth Factor

Bartonella henselae causes vasculoproliferative disorders in humans. We identified a nonfimbrial adhesin of B. henselae designated as Bartonella adhesin A (BadA). BadA is a 340-kD outer membrane protein encoded by the 9.3-kb badA gene. It has a modular structure and contains domains homologous to the Yersinia enterocolitica nonfimbrial adhesin (Yersinia adhesin A). Expression of BadA was restored in a BadA-deficient transposon mutant by complementation in trans. BadA mediates the binding of B. henselae to extracellular matrix proteins and to endothelial cells, possibly via β1 integrins, but prevents phagocytosis. Expression of BadA is crucial for activation of hypoxia-inducible factor 1 in host cells by B. henselae and secretion of proangiogenic cytokines (e.g., vascular endothelial growth factor). BadA is immunodominant in B. henselae–infected patients and rodents, indicating that it is expressed during Bartonella infections. Our results suggest that BadA, the largest characterized bacterial protein thus far, is a major pathogenicity factor of B. henselae with a potential role in the induction of vasculoproliferative disorders.

scholarly journals Hypoxia Inducible Factor-1α Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1359
Author(s):  
Nashwa Amin ◽  
Shijia Chen ◽  
Qiannan Ren ◽  
Xiaoning Tan ◽  
Benson O. A. Botchway ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Hypoxia Inducible Factor ◽  
Mrna Levels ◽  
Endothelin 1 ◽  
Hypoxia Inducible Factor 1 ◽  
I Kappa B Alpha ◽  
Tnf Α

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke.

scholarly journals HIF-1, the Warburg Effect, and Macrophage/Microglia Polarization Potential Role in COVID-19 Pathogenesis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Elisabetta Ferraro ◽  
Maria Germanò ◽  
Rocco Mollace ◽  
Vincenzo Mollace ◽  
Natalia Malara
Keyword(s):  
Potential Role ◽  
Immune Reaction ◽  
Hypoxia Inducible Factor ◽  
Innate Immune ◽  
Metabolic Reprogramming ◽  
Clinical Knowledge ◽  
Respiratory Dysfunction ◽  
Hypoxia Inducible Factor 1 ◽  
Microglia Polarization ◽  
The Warburg Effect

Despite the international scientific community’s commitment to improve clinical knowledge about coronavirus disease 2019 (COVID-19), knowledge regarding molecular details remains limited. In this review, we discuss hypoxia’s potential role in the pathogenesis of the maladaptive immune reaction against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The state of infection, with serious respiratory dysfunction, causes tissues to become hypoxic due to a discrepancy between cellular O2 uptake and consumption similar to that seen within tumor tissue during the progression of numerous solid cancers. In this context, the heterogeneous clinical behavior and the multiorgan deterioration of COVID-19 are discussed as a function of the upregulated expression of the hypoxia-inducible factor-1 (HIF-1) and of the metabolic reprogramming associated with HIF-1 and with a proinflammatory innate immune response activation, independent of the increase in the viral load of SARS-CoV-2. Possible pharmacological strategies targeting O2 aimed to improve prognosis are suggested.

Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia

2009 ◽  
Vol 4 (3) ◽  
pp. 162-173 ◽  
Author(s):  
Penelope Aguilera ◽  
Edgar Vazquez-Contreras ◽  
Carlos Gomez-Martínez ◽  
Maria Cardenas
Keyword(s):  
Cerebral Ischemia ◽  
Therapeutic Target ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Sequential Activation of Hypoxia-Inducible Factor 1 and Specificity Protein 1 is Required for Hypoxia-Induced Transcriptional Stimulation of Abcc8

2011 ◽  
Vol 32 (3) ◽  
pp. 525-536 ◽  
Author(s):  
Seung Kyoon Woo ◽  
Min Seong Kwon ◽  
Zhihua Geng ◽  
Zheng Chen ◽  
Alexander Ivanov ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Binding Sites ◽  
Hypoxia Inducible Factor ◽  
Luciferase Reporter ◽  
Hypoxia Inducible Factor 1 ◽  
Specificity Protein 1 ◽  
Reporter Assays ◽  
Sequential Activation ◽  
Specificity Protein ◽  
Stimulation Of

Cerebral ischemia causes increased transcription of sulfonylurea receptor 1 (SUR1), which forms SUR1-regulated NC(Ca-ATP) channels linked to cerebral edema. We tested the hypothesis that hypoxia is an initial signal that stimulates transcription of Abcc8, the gene encoding SUR1, via activation of hypoxia-inducible factor 1 (HIF1). In the brain microvascular endothelial cells, hypoxia increased SUR1 abundance and expression of functional SUR1-regulated NC(Ca-ATP) channels. Luciferase reporter activity driven by the Abcc8 promoter was increased by hypoxia and by coexpression of HIF1α. Surprisingly, a series of luciferase reporter assays studying the Abcc8 promoter revealed that binding sites for specificity protein 1 (Sp1), but not for HIF, were required for stimulation of Abcc8 transcription by HIF1α. Luciferase reporter assays studying Sp1 promoters of three species, and chromatin immunoprecipitation analysis in rats after cerebral ischemia, indicated that HIF binds to HIF-binding sites on the Sp1 promoter to stimulate transcription of the Sp1 gene. We conclude that sequential activation of two transcription factors, HIF and Sp1, is required to stimulate transcription of Abcc8 following cerebral ischemia. Sequential gene activation in cerebral ischemia provides a plausible molecular explanation for the prolonged treatment window observed for inhibition of the end-target gene product, SUR1, by glibenclamide.

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