scholarly journals Regulation of Spermine Oxidase through Hypoxia-Inducible Factor-1α Signaling in Retinal Glial Cells under Hypoxic Conditions

2020 ◽  
Vol 61 (6) ◽  
pp. 52 ◽  
Author(s):  
Di Wu ◽  
Kousuke Noda ◽  
Miyuki Murata ◽  
Ye Liu ◽  
Atsuhiro Kanda ◽  
...  
Keyword(s):  
Glial Cells ◽  
Hypoxia Inducible Factor ◽  
Spermine Oxidase ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions

scholarly journals Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shion Orikasa ◽  
Nobuyuki Kawashima ◽  
Kento Tazawa ◽  
Kentaro Hashimoto ◽  
Keisuke Sunada-Nara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Dental Pulp Stem Cells ◽  
Pulp Tissue ◽  
Odontoblast Differentiation ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions

AbstractAccelerated dental pulp mineralization is a common complication in avulsed/luxated teeth, although the mechanisms underlying this remain unclear. We hypothesized that hypoxia due to vascular severance may induce osteo/odontoblast differentiation of dental pulp stem cells (DPSCs). This study examined the role of B-cell CLL/lymphoma 9 (BCL9), which is downstream of hypoxia-inducible factor 1α (HIF1α) and a Wnt/β-catenin transcriptional cofactor, in the osteo/odontoblastic differentiation of human DPSCs (hDPSCs) under hypoxic conditions. hDPSCs were isolated from extracted healthy wisdom teeth. Hypoxic conditions and HIF1α overexpression induced significant upregulation of mRNAs for osteo/odontoblast markers (RUNX2, ALP, OC), BCL9, and Wnt/β-catenin signaling target genes (AXIN2, TCF1) in hDPSCs. Overexpression and suppression of BCL9 in hDPSCs up- and downregulated, respectively, the mRNAs for AXIN2, TCF1, and the osteo/odontoblast markers. Hypoxic-cultured mouse pulp tissue explants showed the promotion of HIF1α, BCL9, and β-catenin expression and BCL9-β-catenin co-localization. In addition, BCL9 formed a complex with β-catenin in hDPSCs in vitro. This study demonstrated that hypoxia/HIF1α-induced osteo/odontoblast differentiation of hDPSCs was partially dependent on Wnt/β-catenin signaling, where BCL9 acted as a key mediator between HIF1α and Wnt/β-catenin signaling. These findings may reveal part of the mechanisms of dental pulp mineralization after traumatic dental injury.

Bafilomycin Induces the p21-Mediated Growth Inhibition of Cancer Cells under Hypoxic Conditions by Expressing Hypoxia-Inducible Factor-1α

2006 ◽  
Vol 70 (6) ◽  
pp. 1856-1865 ◽  
Author(s):  
Ji-Hong Lim ◽  
Jong-Wan Park ◽  
Myung-Suk Kim ◽  
Sang-Ki Park ◽  
Randall S. Johnson ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions

Role of Hypoxia and Hypoxia-Inducible-Factor 1α (HIF1A) In the BM Microenvironment-Mediated Protection of Leukemic Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2586-2586
Author(s):  
Rodrigo Jacamo ◽  
Juliana Benito ◽  
Olga Frolova ◽  
Ye Chen ◽  
Hongbo Lu ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Conflicts Of Interest ◽  
Lactic Acid Production ◽  
Hypoxia Inducible Factor ◽  
Leukemic Cells ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions ◽  
Control Mscs ◽  
Culture Supernatants

Abstract Abstract 2586 Resistance to chemotherapy can be mediated by genetic, epigenetic and microenvironmental causes. Only recently the connection between leukemia growth and survival and the hypoxic state of the BM microenvironment has been appreciated, by work conducted by us and others (Fiegl M et.al. Blood 2009; 113: 1504–1512; Harrison JS et. al., Blood 2002; 99). In extension of this concept we investigated the role of Hypoxia-Inducible-Factor 1α (HIF1A), the master regulator of hypoxia induced responses, in the microenvironment and its relevance for leukemia progression. Here we focused on the role of hypoxia and HIF transcription factors in cells contributing to the BM microenvironment, the mesenchymal stromal cells (MSC). Co-culture of lymphoid (NALM6) and myeloid (OCI-AML3) leukemic cell lines with BM-derived MSC under hypoxic conditions (1% O2) stimulated the secretion of a number of pro-survival cytokines and chemokines (including IL-6, VEGF, Beta-NGF and SDF-1α) that were quantified in co-culture supernatants by Luminex flow cytometry (Table 1). These findings suggest that hypoxia, and possibly its main mediator, the transcription factor HIF1A, may be responsible for the increased production of these factors. Since the chemokine stromal cell-derived factor-1α (SDF-1α) is involved in the attraction of leukemic cells towards cells of the BM microenvironment, we next investigated the role of HIF1A expression in MSC and its effect on SDF-1 secretion and migration of leukemic cells under hypoxic conditions. To this end, we generated primary human BM MSC stably transduced with lentiviral-encoded shRNA against HIF1A. SDF-1α transcription levels measured by qRT-PCR were diminished (∼30%, p<0.01) in HIF1A-silenced MSCs compared to control MSCs expressing non-silencing shRNA. This correlated with significantly reduced transwell migration of OCI-AML3 cells towards HIF1A-silenced MSCs compared with control (non-silencing) MSCs (∼35%, p<0.05) under hypoxic conditions. We next examined the contribution of hypoxia and HIF1A in the protective role of the BM microenvironment against standard chemotherapy with AraC and Doxorubicin. To this end, we performed in vitro experiments co culturing OCI-AML3 cells with either HIF1A-silenced MSCs or control MSCs under hypoxic conditions. After 48h of drug treatment a significant decrease in chemotherapy-induced apoptosis in leukemic cells co-cultured with control MSCs compared to leukemic cells cultured alone was observed. In turn, chemoresistance was reduced in OCI-AML3 co-cultured with HIF1A-silenced MSC, suggesting that hypoxia mediates chemoresistance largely through its effects on cells of the BM microenvironment. It has been shown that leukemic cells seem to exhibit increased dependency on glycolysis for ATP generation, which is frequently associated with resistance to therapeutic agents. Therefore, we measured the production of lactic acid (LA) in leukemic cells co-cultured with MSC in hypoxia compared to normoxia. In agreement with previous observations, we found that REH and primary ALL cells produced more LA when they were co-cultured with MSC under hypoxia compared to normoxia (∼1.8 fold, p<0.05). When REH cells were co-cultured with HIF1A-silenced MSCs in hypoxic conditions the lactic acid production was slightly but significantly reduced (∼20%, p<0.05) compared with the values observed in REH-control MSCs co-culture supernatants. Altogether, these findings strongly point to hypoxia and HIF1A as pivotal components in the protection from chemotherapy mediated by the BM microenvironment. We propose that targeting HIF1A and hypoxia in the protective cells of the bone marrow niches may represent a new approach to increase chemosensitivity of leukemic cells and hopefully improve the existing therapeutic strategies. Table 1: Fold increase observed in leukemic cells-MSC co-culture supernatants in hypoxia compared to normoxia. OCI-AML3+MSC NALM6+MSC IL-6 ∼3.1 ∼1.2 VEGF ∼3 ∼2 B-NGF ∼8 ∼10 SDF-1 ∼1.5 ∼1.5 Disclosure: No relevant conflicts of interest to declare.

scholarly journals Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions

Epigenetics ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. 600-610 ◽  
Author(s):  
Laura Tudisco ◽  
Floriana Della Ragione ◽  
Valeria Tarallo ◽  
Ivana Apicella ◽  
Maurizio D'Esposito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Placental Growth Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Epigenetic Control ◽  
Hypoxic Conditions

scholarly journals Efficient translation of mouse hypoxia-inducible factor-1α under normoxic and hypoxic conditions

2000 ◽  
Vol 1493 (1-2) ◽  
pp. 125-134 ◽  
Author(s):  
Agnes Görlach ◽  
Gieri Camenisch ◽  
Ivica Kvietikova ◽  
Lorenz Vogt ◽  
Roland H. Wenger ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions

Pharmacological stimulation of soluble guanylate cyclase modulates hypoxia-inducible factor-1α in rat heart

2009 ◽  
Vol 297 (4) ◽  
pp. H1274-H1280 ◽  
Author(s):  
Toshihiro Tsuruda ◽  
Kinta Hatakeyama ◽  
Hiroyuki Masuyama ◽  
Yoko Sekita ◽  
Takuroh Imamura ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Mechanical Load ◽  
Hypoxia Inducible Factor ◽  
Pressure Overload ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions ◽  
Cgmp Analog ◽  
Male Wistar Rats ◽  
Cultured Cardiomyocytes

Mechanical load and ischemia induce a series of adaptive physiological responses by activating the expression of O2-regulated genes, such as hypoxia inducible factor-1α (HIF-1α). The aim of this study was to explore the interaction between HIF-1α and soluble guanylate cyclase (sGC) and its second messenger cGMP in cultured cardiomyocytes exposed to hypoxia and in pressure-overloaded heart. In cultured cardiomyocytes of neonatal rats, either sGC stimulator BAY 41-2272 or cGMP analog 8-bromo-cGMP decreased the hypoxia (1% O2/5% CO2)-induced HIF-1α expression, whereas the inhibition of protein kinase G by KT-5823 reversed the effect of BAY 41-2272 on the expression under hypoxic conditions. In pressure-overloaded heart induced by suprarenal aortic constriction (AC) in 7-wk-old male Wistar rats, the administration of BAY 41-2272 (2 mg·kg−1·day−1) for 14 days significantly suppressed the protein expression of HIF-1α ( P < 0.05), vascular endothelial growth factor ( P < 0.01), and the number of capillary vessels ( P < 0.01) induced by pressure overload. This study suggests that the pharmacological sGC-cGMP stimulation modulates the HIF-1α expression in response to hypoxia or mechanical load in the heart.

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