Differential contribution of key metabolic substrates and cellular oxygen in HIF signalling

Zhdanov, Alexander V.; Waters, Alicia; Golubeva, Anna V.; Papkovsky, Dmitri B.

doi:10.1016/j.yexcr.2014.10.005

Cited by 25 publications

(21 citation statements)

References 88 publications

(119 reference statements)

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“…By contrast, glutamine is metabolized in human B-cell lymphoma model cells cultured in hypoxia largely via forward TCA cycling, with only a minor amount undergoing reductive carboxylation 151 . HIFα stabilization can occur independently of hypoxia in tumors owing to mutations in factors involved in the degradation of HIFα subunits (such as von Hippel Lindau tumor suppressor (VHL)) 159 or through increased translation through mTOR 161 , and glutamine itself can also increase HIFα stabilization 162–164 . We suspect that as more genes and tissues are studied, glutamine metabolism will be found to be reprogrammed through modulation of the pathways described above (Table 1) and through novel direct mechanisms.…”

Section: Oncogenes and Glutamine Metabolismmentioning

confidence: 99%

From Krebs to clinic: glutamine metabolism to cancer therapy

2016

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The resurgence of research in cancer metabolism has recently broadened interests beyond glucose and the Warburg Effect to other nutrients including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.

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Section: Oncogenes and Glutamine Metabolismmentioning

confidence: 99%

From Krebs to clinic: glutamine metabolism to cancer therapy

2016

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“…The hypoxia-inducible factor (HIF) pathway has been considered a powerful stimulus under a variety of pathological conditions by influencing angiogenesis and cellular metabolism [24,25]. A set of hypoxia-regulated microRNAs were identified under hypoxic stress and provided an approach to understand the relation between stress factors and gene expression control [16,26,27].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced MicroRNA-429 Promotes Differentiation of MC3T3-E1 Osteoblastic Cells by Mediating ZFPM2 Expression

Huang

Peng

Cao

et al. 2016

Cell Physiol Biochem

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Background/Aims: Hypoxia has been reported to regulate osteoblastic differentiation of bone cells and cartilage development. However, information concerning the molecular mechanisms remains largely unknown. Methods: The expression of miR-429 was evaluated by quantitative real-time PCR analysis. To test whether miR-429 directly regulate the expression level of ZFPM2 at transcription level, dual-luciferase reporter gene assay was performed. Western blotting was performed to detect osteogenesis related protein expression. The cell proliferation, apoptosis, alkaline phosphatase activity and matrix mineralization were performed to assess the functions of miR-429 in vitro and in vivo the effects of miR-429 on fracture healing. Results: Expression of miR-429 was increased in MC3T3-E1 cells treated with 200 μM CoCl₂ by qRT-PCR, and overexpression of miR-429 promoted cell differentiation, and enhanced alkaline phosphatase activity and matrix mineralization. Luciferase reporter assays suggested that miR-429 directly targets the 3'UTR of ZFPM2. In addition, knockdown of ZFPM2 could phenocopy the effects of miR-429 expression. Furthermore, overexpression of ZFPM2 in miR-429-expressing MC3T3-E1 cells suppressed cell differentiation. Conclusions: Our results provide valuable insight into the potential role of hypoxia in regulation of osteoblastic cell differentiation.

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“…By contrast, glutamine is metabolized in human B-cell lymphoma model cells cultured in hypoxia largely via forward TCA cycling, with only a minor amount undergoing reductive carboxylation 151 . HIFα stabilization can occur independently of hypoxia in tumors owing to mutations in factors involved in the degradation of HIFα subunits (such as von Hippel Lindau tumor suppressor (VHL)) 159 or through increased translation through mTOR 161 , and glutamine itself can also increase HIFα stabilization [162][163][164] . We suspect that as more genes and tissues are studied, glutamine metabolism will be found to be reprogrammed through modulation of the pathways described above (Table 1) and through novel direct mechanisms.…”

Section: Oncogenes and Glutamine Metabolismmentioning

confidence: 99%