Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1

Neuroscience ◽  
2004 ◽  
Vol 126 (2) ◽  
pp. 433-440 ◽  
Author(s):  
B Zhang ◽  
J Tanaka ◽  
L Yang ◽  
L Yang ◽  
M Sakanaka ◽  
...  
Keyword(s):  
Vitamin E ◽  
Protective Effect ◽  
Brain Ischemia ◽  
Neuronal Death ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Focal Brain Ischemia

Delayed Neuronal Death Following Acute Focal Brain Ischemia

2003 ◽  
pp. 101-102
Author(s):  
Eugene Gusev ◽  
Veronica I. Skvortsova
Keyword(s):  
Brain Ischemia ◽  
Neuronal Death ◽  
Delayed Neuronal Death ◽  
Focal Brain Ischemia

scholarly journals An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia

2009 ◽  
Vol 37 (14) ◽  
pp. 4587-4602 ◽  
Author(s):  
Yair Benita ◽  
Hirotoshi Kikuchi ◽  
Andrew D. Smith ◽  
Michael Q. Zhang ◽  
Daniel C. Chung ◽  
...  
Keyword(s):  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Integrative Genomics ◽  
Hypoxia Inducible Factor 1 ◽  
The Core

scholarly journals Hypoxia-Inducible Factor-1 (Hif-1) in Experimental Brain Ischemia

2002 ◽  
Vol 2 ◽  
pp. 123-124 ◽  
Author(s):  
Rainald Schmidt-Kastner ◽  
Bao-Tong Zhang ◽  
Keith Webster ◽  
Thomas Kietzmann ◽  
Weizhao Zhao ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

Hypoxia-Inducible Factor-1 in Multiple Myeloma Progression.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1812-1812
Author(s):  
Roberto Ria ◽  
Antonia Reale ◽  
Simona Berardi ◽  
Claudia Piccoli ◽  
Giulia Di Pietro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Endothelial Cells ◽  
Target Genes ◽  
Plasma Cells ◽  
Hypoxia Inducible Factor ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vegf Receptor ◽  
Rt Pcr ◽  
Hypoxia Inducible Factor 1

Abstract Abstract 1812 Poster Board I-838 Multiple Myeloma (MM) is a malignancy of immunoglobulin (Ig)-synthesizing plasma cells, that home to and expand in the bone marrow. Similarly to other tumours its development is correlated to the formation of regions of hypoxia, which may be a prognostic indicator and determinant of malignant progression. It is known how in solid tumours the degree of intra-tumoral hypoxia is positively correlated with the expression of the transcription factor hypoxia-inducible factor 1 (HIF-1). HIF-1 is composed of HIF-1á and HIF-1β subunits and its production has been identified as a key element in allowing cells to adapt and survive in a hostile hypoxic environment via a variety of pathways. In hypoxia conditions, the HIF-1á subunit becomes stable and regulates the expression of target genes. When activated HIF-1á also targets those genes which are required for angiogenesis, the development of new blood vessels from an existing vascular network. Angiogenesis represents a constant hallmark of MM progression. In response to hypoxia plasma cells and stromal cells (endothelial cells [ECs], macrophages, mast cells) within the tumour express Vascular Endothelial Growth Factor (VEGF), a mitogen and survival factor specific for endothelial cells. VEGF is the major regulator of tumor-associated angiogenesis. HIF-1á directly activates transcription of the VEGF gene and this leads to autocrine signal transduction that is critical for angiogenesis. In this study we demonstrate the role of HIF-1á in MM angiogenesis. The constitutive stabilization of HIF-1á contributes to increase angiogenesis in MM. Our data show that HIF-1á is stabilized in the nucleus of MM endothelial cells (MMECs) but not in ECs of Monoclonal Gammopathies of Undetermined Significance (MGECs) and in Human Umbilical Vein ECs (HUVECs) used as controls. Western Blot and Enzyme-Linked Immunosorbent Assay (ELISA) analyses show the overexpression of HIF-1á and the proteic products of its target genes VEGF and VEGF Receptor (VEGFR)-1, in patients with relapsed disease and in MM progression but not in patients with nonactive MM (avascular phase). Moreover, immunofluorescent staining confirm the nuclear stabilization of HIF-1á in MMECs. At mRNA level all ECs express same quantity of HIF-1á mRNA, as confirmed by RT-PCR and Real-time RT-PCR, indicating that in MMECs the post-trascriptional control is affected. Finally, we show that the inhibition of HIF-1á by siRNA suppresses vessel formation in vitro and promote ECs apoptosis. Our findings indicate that HIF-1á plays an important role in MM progression and that it is correlated to the angiogenic switch from nonactive MM to active MM. Furthermore these data suggest that HIF-1á may represent a target for the MM antiangiogenic treatment. Disclosures No relevant conflicts of interest to declare.

Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain

1999 ◽  
Vol 11 (12) ◽  
pp. 4159-4170 ◽  
Author(s):  
Marcelle Bergeron ◽  
Aimee Y. Yu ◽  
Karen E. Solway ◽  
Gregg L. Semenza ◽  
Frank R. Sharp
Keyword(s):  
Rat Brain ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Focal Ischaemia

scholarly journals Intermittent hypoxia enhances the expression of HIF1A by increasing the quantity and catalytic activity of KDM4A-C and demethylating H3K9me3 at the HIF1A locus

2021 ◽  
Author(s):  
Chloe-Anne Martinez ◽  
Neha Bal ◽  
Peter A Cistulli ◽  
Kristina M Cook
Keyword(s):  
Intermittent Hypoxia ◽  
Target Genes ◽  
Chronic Hypoxia ◽  
Oxygen Sensing ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Sensing Systems ◽  
Cellular Oxygen ◽  
Fine Tune

Cellular oxygen-sensing pathways are primarily regulated by hypoxia inducible factor-1 (HIF-1) in chronic hypoxia and are well studied. Intermittent hypoxia also occurs in many pathological conditions, yet little is known about its biological effects. In this study, we investigated how two proposed cellular oxygen sensing systems, HIF-1 and KDM4A-C, respond to cells exposed to intermittent hypoxia and compared to chronic hypoxia. We found that intermittent hypoxia increases HIF-1 activity through a pathway distinct from chronic hypoxia, involving the KDM4A, -B and -C histone lysine demethylases. Intermittent hypoxia increases the quantity and activity of KDM4A-C resulting in a decrease in H3K9 methylation. This contrasts with chronic hypoxia, which decreases KDM4A-C activity, leading to hypermethylation of H3K9. Demethylation of histones bound to the HIF1A gene in intermittent hypoxia increases HIF1A mRNA expression, which has the downstream effect of increasing overall HIF-1 activity and expression of HIF target genes. This study highlights how multiple oxygen-sensing pathways can interact to regulate and fine tune the cellular hypoxic response depending on the period and length of hypoxia.

scholarly journals Hypoxic Preconditioning Induces Changes in HIF-1 Target Genes in Neonatal Rat Brain

2001 ◽  
Vol 21 (9) ◽  
pp. 1105-1114 ◽  
Author(s):  
Nicole M. Jones ◽  
Marcelle Bergeron
Keyword(s):  
Gene Expression ◽  
Rat Brain ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Preconditioning ◽  
Neonatal Rat ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Hypoxia Inducible Factor 1 ◽  
Neonatal Rat Brain

Hypoxic preconditioning induces tolerance to hypoxic-ischemic injury in neonatal rat brain and is associated with changes in gene expression. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that is strongly induced by hypoxia or the hypoxia-mimetic compound cobalt chloride (CoCl2). Hypoxia-inducible factor-1 modulates the expression of several target genes including the glycolytic enzymes, glucose transporter-1 (GLUT-1), and erythropoietin. Recently, HIF-1 expression was shown to increase after hypoxic and CoCl2 preconditioning in newborn rat brain. To study the involvement of HIF-1 target genes in neonatal hypoxia-induced ischemic tolerance, the authors examined the brains of newborn rats after exposure to hypoxia (8% O2 for 3 hours) or injection of CoCl2 (60 mg/kg). Preconditioning with hypoxia or CoCl2 24 hours before hypoxia-ischemia afforded a 96% and 76% brain protection, respectively, compared with littermate control animals. Hypoxic preconditioning increased the expression of GLUT-1 mRNA and protein, and of aldolase, phosphofructokinase, and lactate dehydrogenase proteins but not mRNA. This suggests that the modulation of glucose transport and glycolysis by hypoxia may contribute to the development of hypoxia-induced tolerance. In contrast, preconditioning with CoCl2 did not produce any change in HIF-1 target gene expression suggesting that different molecular mechanisms may be involved in the induction of tolerance by hypoxia and CoCl2 in newborn brain.

scholarly journals Cathepsin L, a Target of Hypoxia-Inducible Factor-1-α, Is Involved in Melanosome Degradation in Melanocytes

2021 ◽  
Vol 22 (16) ◽  
pp. 8596
Author(s):  
Ji Young Kim ◽  
Eun Jung Lee ◽  
Yuri Ahn ◽  
Sujin Park ◽  
Yu Jeong Bae ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Cathepsin L ◽  
Hypoxia Inducible Factor ◽  
Luciferase Reporter ◽  
Lysosomal Activity ◽  
Hypoxia Inducible Factor 1 ◽  
Lysosomal Protease ◽  
Hypoxic Conditions ◽  
Novel Target

Hypoxic conditions induce the activation of hypoxia-inducible factor-1α (HIF-1α) to restore the supply of oxygen to tissues and cells. Activated HIF-1α translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1α, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-α at its promoter. Under autophagy-inducing starvation conditions, HIF-1α and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome–lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1α, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome–lysosome fusion.

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