The magic of the hypoxia-signaling cascade

Benizri, Emmanuel; Ginouvès, Amandine; Berra, Edurne

doi:10.1007/s00018-008-7472-0

Cited by 84 publications

(74 citation statements)

References 156 publications

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“…HIF 1-A gets increased, which promotes binding to HIF-1B. The complex will initiate multiple gene transcription so RNA polymerase II activity is activated [15] [16]. Therefore, HIF-1 causes an increment of the expression of multiple factors: placental growth factor (PLGF), vascular endotelial growth factor (VEGF), platelet derived growth factor (PDGF) or erythropoietin (EPO).…”

Section: Changes In Gene Expression: the Role Of Hypoxia Inducible Famentioning

confidence: 99%

Oxygen Therapy in Critical Care: A Double Edged Sword

Portillo¹,

Vázquez²,

Mendoza³

et al. 2014

Health

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The oxygen therapy is an universal treatment in the hospital setting, especially in the critical care units. The purpose of this therapy is to avoid hypoxemia and to ensure an adequate supply of oxygen to the tissues. But often we overlook the potential adverse effects of oxygen therapy. Oxygen produces lung damage and induces apoptosis and cell death creating an imbalance between the production of reactive species of oxygen and the antioxidant mechanisms. The oxygen therapy inhibits systemic adaptive changes induced by hypoxia, disrupting compensatory mechanisms and causing deleterious effects. We are faced with a challenge in order to treat patients with respiratory failure, counterbalancing hypoxia with hyperoxia-induced damage and introducing therapy lines that are innovative but not risk-free as permissive hypoxemia. Currently many questions remain unresolved and there are not enough clinical studies that validate the therapeutic optimal oxygenation ranges. These ranges may differ depending on each patient and the underlying disease.

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Section: Changes In Gene Expression: the Role Of Hypoxia Inducible Famentioning

confidence: 99%

Oxygen Therapy in Critical Care: A Double Edged Sword

Portillo¹,

Vázquez²,

Mendoza³

et al. 2014

Health

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“…Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates [1,2], and the elucidation of the mechanisms of carcinogenesis and tumor progression has contributed to the development of novel treatment strategies. The disordered and accelerated proliferation of neoplastic cells during tumorigenesis and tumor progression reduces oxygen and nutrient supply, thereby generating a microenvironment characterized by hypoxia, necrosis and inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Hypoxia promotes inflammation, and the inflamed tissues become even more hypoxic. Under normal oxygen concentrations, HIF (hypoxia-inducible factor) is inactive; however, HIF1A (hypoxia-inducible factor 1-alpha) is activated in response to hypoxia in the tumor microenvironment [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

et al. 2017

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Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08-6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients.

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“…Adaptation to reduced oxygen availability is indeed a major physiological challenge during embryonic development and in adulthood, but it is also associated with many human diseases (Benizri et al, 2008). This adaptation is primarily led by activation of hypoxia inducible factor (HIF), which controls the expression of hundreds of direct target genes, secondary transcription factors and non-coding RNAs (Semenza, 2012).…”

Section: Introductionmentioning

confidence: 99%

PHD3-SUMO conjugation optimizes HIF1 repression independently of PHD3 catalytic activity

Núñez-O'Mara

Gerpe-Pita

Pozo

et al. 2014

Journal of Cell Science

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By controlling HIFa hydroxylation and stability, the prolyl hydroxylase domain (PHD)-containing proteins are essential to the maintenance of oxygen homeostasis; therefore these enzymes are tightly regulated. Small ubiquitin-like modifier (SUMO) is a 10-kDa protein readily conjugated to lysine residues of the targeted proteins in a process termed SUMOylation. In this study, we introduce SUMO conjugation as a novel regulator of PHD3 (also known as EGLN3). PHD3 SUMOylation occurs at a cluster of four lysines at the C-terminal end of the protein. Furthermore, PHD3 SUMOylation by SUMO2 or SUMO3 contributes to PHD3-mediated repression of HIF1-dependent transcriptional activity. Interestingly, PHD3-SUMO conjugation does not affect PHD3 hydroxylase activity or HIF1a stability, providing new evidence for a dual role of PHD3 in HIF1 regulation. Moreover, we show that hypoxia modulates PHD3-SUMO conjugation and that this modification inversely correlates with HIF1 activation. PHD3 SUMOylation highlights a new and additional layer of regulation that is likely required to fine-tune HIF function.

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The magic of the hypoxia-signaling cascade

Cited by 84 publications

References 156 publications

Oxygen Therapy in Critical Care: A Double Edged Sword

Oxygen Therapy in Critical Care: A Double Edged Sword

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

PHD3-SUMO conjugation optimizes HIF1 repression independently of PHD3 catalytic activity

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