Evaluation of hypoxia inducible factor expression in inflammatory and neurodegenerative brain models

Lemos, Maria Luisa de; Torre, Aurelio Vázquez de la; Petrov, Dimitry; Brox, Susana; Folch, Jaume; Pallàs, Mercè; Lazarowski, Alberto; Beas‐Zárate, Carlos; Auladell, Carme; Camins, Antoni

doi:10.1016/j.biocel.2013.04.011

Cited by 43 publications

(31 citation statements)

References 61 publications

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“…According with these observations, we could speculate that the high expression of these 3 markers in SEGA cells from non-vascularized areas of the tumor, suggest a link with the hypoxic condition, as a prone scenario for the annealing and growth of stem cells expressing these markers. In this regard, it is important to notice that brain expression of P-gp and BCRP genes are also related with hypoxic and/or inflammatory conditions [58][59][60][61] .…”

Section: Discussionmentioning

confidence: 99%

CD34 stem-cell marker and multidrug resistance proteins P-gp and BCRP in SEGA

Lazarowski

Fabiana²,

Sandra³

et al. 2014

Receptor Clin Invest

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The resistance of human malignancy to multiple chemotherapeutic agents remains a major obstacle in cancer therapy due to in part to increased expression of ATP-binding cassette (ABC) transporters gene family, including "multidrug resistance 1", and "breast cancer resistant protein". These proteins are differentially expressed during normal hematopoiesis with the highest levels in primitive bone marrow CD34 stem cell population, and similarly, it was also suggested to occur transiently during neurulation. Subependymal Giant Cell Astrocytoma (SEGA) is a periventricular-low-grade tumor usually associated with tuberous sclerosis complex. We previously described that several multidrug-resistance proteins are overexpressed in brain cortical tubers associated with refractory epilepsy; however, they have not been investigated in SEGA. From a previous reported study of 15 brain specimens of SEGA, 6 randomized cases were selected for the immunostaining with specific monoclonal antibodies to multidrug resistance 1, breast cancer resistant protein and CD34 stem-cell marker. Heterogeneous distributions for these markers were detected with differential immunostaining pattern, showing high immunoreactivity in SEGA cells far of vessels, and low or negative expression in SEGA cells near the vessels. This particular expression pattern of both ABCtransporters, and CD34 antigen could identify different stem-cell subset in SEGA.Keywords: CD34; P-gp; BCRP; SEGA; Hypoxia; Tuberous Sclerosis; Stem-Cell To cite this article: Alberto L, et al. Stem-cell marker CD34, multidrug resistance proteins P-gp and BCRP in SEGA.

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Section: Discussionmentioning

confidence: 99%

CD34 stem-cell marker and multidrug resistance proteins P-gp and BCRP in SEGA

Lazarowski

Fabiana²,

Sandra³

et al. 2014

Receptor Clin Invest

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“…Hypoxia-inducible factor 1 (HIF-1) is an important regulator under conditions of hypoxia (10) and is also important in controlling the neurological outcomes following ischemic stroke due to its ability to regulate a variety of genes (11). HIF-1α is degraded in cells under normoxic conditions, however is significantly upregulated during hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Role of hypoxia-inducible factor-1α in autophagic cell death in microglial cells induced by hypoxia

Wang

et al. 2017

Molecular Medicine Reports

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Microglial cells are phagocytic cells of the central nervous system (CNS) and have been proposed to be a primary component of the innate immune response and maintain efficient CNS homeostasis. Microglial cells are activated during various phases of tissue repair and participate in various pathological conditions in the CNS. Following spinal cord injury (SCI), anoxemia is a key problem that results in tissue destruction. Hypoxia-inducible factor 1-α (HIF-1α) may protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. However, numerous studies have revealed that hypoxia upregulates HIF-1α expression leading to the death of microglial cells. The present study investigated the alterations in HIF-1α expression levels and the mechanism of autophagic cell death mediated by HIF-1α in microglial cells induced by hypoxia. Hypoxia was demonstrated to induce HIF-1α expression and autophagic cell death in microglial cells. Enhanced autophagy reduced cell death during the initial stages by restraining the functions of autophagy-associated genes (microtubule-associated protein 1A/1B-light chain 3 phosphatidylethanolamine conjugate and Beclin-1) and modulating the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Target value was determined by Cell Counting Kit 8 and cell death by flow cytometry. Transmission electron microscopy, immunohistochemical staining, reverse transcription-quantitative polymerase chain reaction, western blotting, and ELISA were used for further analysis. However, increased expression of HIF-1α induced cell death and autophagic cell death in microglial cells. Furthermore, the effects of the HIF-1α inhibitor 2-methoxyestradiol and HIF-1α small interfering RNA on the death and autophagy of microglial cells in vitro were investigated. These investigations revealed the suppression of autophagy, the decrease of cell viability and the increase of inflammatory cytokines results from HIF-1α inhibition or HIF-1α silencing. In conclusion, the results indicated that appropriate expression of HIF-1α can ameliorate autophagic cell death of microglial cells associated with hypoxia, and may provide a novel therapeutic approach for SCI associated with microglial cell activation.

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“…While in hypoxic conditions, HIF1a accumulates and plays a role in the transcriptional regulation of hypoxia-inducible genes involved in angiogenesis, metabolism, apoptosis, and cellular stress [2;3]. HIF1a is also increased following several pathological conditions, including acute neuroinflammation [4;5] and increased mTORC1 activity in mice and humans independent of hypoxia [6–10]. The function of HIF1a in hyperactive mTORC1 has been shown to increase neuron survival [6].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor-1a contributes to dendritic overgrowth in tuberous sclerosis

Zhang

Feliciano

Huang

et al. 2016

Neuroscience Letters

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Expression of hypoxia-inducible factor 1a (HIF1a) is increased under several pathological conditions such as hyperactive mechanistic target of rapamycin complex 1 (mTORC1) in tuberous sclerosis complex (TSC). Hyperactive mTORC1 and the resulting increased dendritic complexity of neurons are shared molecular and cellular alterations in several neurological disorders associated with cognitive disabilities. Despite some evidence that HIF1a contributes to dendritic overgrowth in vitro, it remains unknown whether increased HIF1a in TSC neurons could contribute to their increased dendritic complexity. To address this use in vivo, we generated TSC neurons by deleting Tsc1 in newborn olfactory bulb (OB) neurons of conditional Tsc1 transgenic mice using neonatal electroporation. In addition to their increased dendritic complexity, Tsc1null neurons have been reported to display increased Hif1a mRNA level and HIF1a transcriptional activity. We found that Tsc1null-dependent dendritic overgrowth was prevented by knocking down HIF1a or expressing a dominant negative HIF1a. In addition, overexpressing HIF1a in wild-type developing neurons resulted in increased dendritic complexity in vivo. These data highlight that an increase in HIF1a levels contributes to abnormal dendritic patterning in developing neurons under normal condition and hyperactive mTORC1 condition as in TSC.3

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Evaluation of hypoxia inducible factor expression in inflammatory and neurodegenerative brain models

Cited by 43 publications

References 61 publications

CD34 stem-cell marker and multidrug resistance proteins P-gp and BCRP in SEGA

CD34 stem-cell marker and multidrug resistance proteins P-gp and BCRP in SEGA

Role of hypoxia-inducible factor-1α in autophagic cell death in microglial cells induced by hypoxia

Hypoxia-inducible factor-1a contributes to dendritic overgrowth in tuberous sclerosis

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