The Effect of Hypoxia on the Expression of 150 kDa Oxygen-regulated Protein (ORP 150) in HeLa Cells

Cechowska-Pasko, Marzanna; Bańkowski, Edward; Chêne, Patrick

doi:10.1159/000091467

Cited by 24 publications

(16 citation statements)

References 32 publications

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“…4) lies less than 1 kb away from a candidate gene for hypoxia-adaptations, hypoxia up-regulated protein 1 ( HYOU1 ), which encodes a molecular chaperone induced in the endoplasmic reticulum under hypoxic condition 27,28 (Supplementary Fig. 13).…”

Section: Resultsmentioning

confidence: 99%

Admixture facilitates genetic adaptations to high altitude in Tibet

et al. 2014

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Admixture is recognized as a widespread feature of human populations, renewing interest in the possibility that genetic exchange can facilitate adaptations to new environments. Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower hemoglobin concentration. However, the history of these variants or that of Tibetans remains poorly understood. Here, we analyze genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders. Accordingly, the Sherpa and Tibetans share adaptive hemoglobin traits. This admixture-mediated adaptation shares important features with adaptive introgression. Therefore, we identify a novel mechanism, beyond selection on new mutations or on standing variation, through which populations can adapt to local environments.

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Section: Resultsmentioning

confidence: 99%

Admixture facilitates genetic adaptations to high altitude in Tibet

et al. 2014

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“…HYOU1/ORP-150 belongs to heat shock protein 70 family and plays an important role in protein folding and secretion in the ER [58], [59]. Suppression of HYOU1/ORP150 expression leads to accelerated apoptosis [60]. Physical interaction between HIV-1 gp120 and HYOU1 was observed in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses [61].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Vpr Modulates Macrophage Metabolic Pathways: A SILAC-Based Quantitative Analysis

et al. 2013

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Human immunodeficiency virus type 1 encoded viral protein Vpr is essential for infection of macrophages by HIV-1. Furthermore, these macrophages are resistant to cell death and are viral reservoir. However, the impact of Vpr on the macrophage proteome is yet to be comprehended. The goal of the present study was to use a stable-isotope labeling by amino acids in cell culture (SILAC) coupled with mass spectrometry-based proteomics approach to characterize the Vpr response in macrophages. Cultured human monocytic cells, U937, were differentiated into macrophages and transduced with adenovirus construct harboring the Vpr gene. More than 600 proteins were quantified in SILAC coupled with LC-MS/MS approach, among which 136 were significantly altered upon Vpr overexpression in macrophages. Quantified proteins were selected and clustered by biological functions, pathway and network analysis using Ingenuity computational pathway analysis. The proteomic data illustrating increase in abundance of enzymes in the glycolytic pathway (pentose phosphate and pyruvate metabolism) was further validated by western blot analysis. In addition, the proteomic data demonstrate down regulation of some key mitochondrial enzymes such as glutamate dehydrogenase 2 (GLUD2), adenylate kinase 2 (AK2) and transketolase (TKT). Based on these observations we postulate that HIV-1 hijacks the macrophage glucose metabolism pathway via the Vpr-hypoxia inducible factor 1 alpha (HIF-1 alpha) axis to induce expression of hexokinase (HK), glucose-6-phosphate dehyrogenase (G6PD) and pyruvate kinase muscle type 2 (PKM2) that facilitates viral replication and biogenesis, and long-term survival of macrophages. Furthermore, dysregulation of mitochondrial glutamate metabolism in macrophages can contribute to neurodegeneration via neuroexcitotoxic mechanisms in the context of NeuroAIDS.

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“…This suggests that ORP150 mRNA expression is delayed, as based on the Hypoxyprobe results, the cells become hypoxic from 16 h. Notably, ORP150 expression reduced over time under normoxic and hypoxic conditions. Unlike additionally cell types including Hela cells (49), neuronal cells (50)(51)(52), renal cells (53) and cardiomyocytes (54,55), in MLO-Y4 cells ORP150 does not appear to be regulated by hypoxia at early time points. Similar results were identified for the ORP150 protein expression in pre-osteoblasts grown under hypoxic conditions compared with normoxic conditions.…”

Section: Discussionmentioning

confidence: 82%

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

Montesi

Jähn

Bonewald

et al. 2016

Molecular Medicine Reports

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Abstract. Skeletal unloading leads to hypoxia in the bone microenvironment, resulting in imbalanced bone remodeling that favors bone resorption. Osteocytes, the mechanosensors of bone, have been demonstrated to orchestrate bone homeostasis. Hypoxic osteocytes either undergo apoptosis or actively stimulate osteoclasts to remove bone matrix during hypoxia. Oxygen-regulated protein 150 (ORP150) is an endoplasmic reticulum-associated chaperone that has been observed to serve an important role in the cellular adaptation to hypoxia and in preventing cellular apoptosis in various tissue types. The current study hypotheses that expression of ORP150 would be increased in osteocytes under hypoxic conditions (1% O 2 ). The MLO-Y4 osteocyte cell line was cultured under normoxic or hypoxic conditions for up to 72 h. It was demonstrated that 1% O 2 significantly induced hypoxia after 16 h and up to 72 h, significantly reduced cell number at 8 and 48 h, induced cell death at 8, 24 and 48 h and induced apoptosis at 16, 24 and 48 h. Significant differences in ORP150 mRNA were observed at 72 h, however no differences were observed in the protein expression levels. The relative increase in ORP150 mRNA observed in hypoxia, compared with normoxia, may support its cytoprotective role in oxygen-deprived conditions.

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The Effect of Hypoxia on the Expression of 150 kDa Oxygen-regulated Protein (ORP 150) in HeLa Cells

Cited by 24 publications

References 32 publications

Admixture facilitates genetic adaptations to high altitude in Tibet

Admixture facilitates genetic adaptations to high altitude in Tibet

HIV-1 Vpr Modulates Macrophage Metabolic Pathways: A SILAC-Based Quantitative Analysis

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

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