Mammalian Tissue Oxygen Levels Modulate Iron-Regulatory Protein Activities in Vivo

Science ◽  
2004 ◽  
Vol 306 (5704) ◽  
pp. 2087-2090 ◽  
Author(s):  
E. G. Meyron-Holtz
Keyword(s):  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Mammalian Tissue ◽  
Tissue Oxygen ◽  
Oxygen Levels

In vivo Monitoring of Oxygen Levels in Human Brain Tumor Between Fractionated Radiotherapy Using Oxygen-enhanced MR Imaging

2020 ◽  
Vol 16 (4) ◽  
pp. 427-432
Author(s):  
Junchao Qian ◽  
Xiang Yu ◽  
Bingbing Li ◽  
Zhenle Fei ◽  
Xiang Huang ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Tumor Cells ◽  
Normal Tissue ◽  
Oxygen Level ◽  
Tissue Oxygen ◽  
Human Brain Tumor ◽  
Fractionated Radiotherapy ◽  
Oxygen Levels ◽  
Oxygen Breathing

Background:: It was known that the response of tumor cells to radiation is closely related to tissue oxygen level and fractionated radiotherapy allows reoxygenation of hypoxic tumor cells. Non-invasive mapping of tissue oxygen level may hold great importance in clinic. Objective: The aim of this study is to evaluate the role of oxygen-enhanced MR imaging in the detection of tissue oxygen levels between fractionated radiotherapy. Methods: A cohort of 10 patients with brain metastasis was recruited. Quantitative oxygen enhanced MR imaging was performed prior to, 30 minutes and 22 hours after first fractionated radiotherapy. Results: The ΔR1 (the difference of longitudinal relaxivity between 100% oxygen breathing and air breathing) increased in the ipsilateral tumor site and normal tissue by 242% and 152%, respectively, 30 minutes after first fractionated radiation compared to pre-radiation levels. Significant recovery of ΔR1 in the contralateral normal tissue (p < 0.05) was observed 22 hours compared to 30 minutes after radiation levels. Conclusion: R1-based oxygen-enhanced MR imaging may provide a sensitive endogenous marker for oxygen changes in the brain tissue between fractionated radiotherapy.

Effect of acute hypoxia on microcirculatory and tissue oxygen levels in rat cremaster muscle

2005 ◽  
Vol 98 (4) ◽  
pp. 1177-1184 ◽  
Author(s):  
Paul C. Johnson ◽  
Kim Vandegriff ◽  
Amy G. Tsai ◽  
Marcos Intaglietta
Keyword(s):  
Acute Hypoxia ◽  
Hypoxic Exposure ◽  
Cremaster Muscle ◽  
Tissue Oxygen ◽  
Oxygen Levels ◽  
Oxygen Fraction ◽  
Arterial Blood ◽  
S Period ◽  
Inspired Oxygen

Repeated exposure to brief periods of hypoxia leads to pathophysiological changes in experimental animals similar to those seen in sleep apnea. To determine the effects of such exposure on oxygen levels in vivo, we used an optical method to measure Po2 in microcirculatory vessels and tissue of the rat cremaster muscle during a 1-min step reduction of inspired oxygen fraction from 0.21 to 0.07. Under control conditions, Po2 was 98.1 ± 1.9 Torr in arterial blood, 52.2 ± 2.8 Torr in 29.0 ± 2.7-μm arterioles, 26.8 ± 1.7 Torr in the tissue interstitium near venous capillaries, and 35.1 ± 2.6 Torr in 29.7 ± 1.9-μm venules. The initial fall in Po2 during hypoxia was significantly greater in arterial blood, being 93% complete in the first 10 s, whereas it was 68% complete in arterioles, 47% at the tissue sites, and 38% in venules. In the 10- to 30-s period, the fall in normalized tissue and venular Po2 was significantly greater than in arterial Po2. At the end of hypoxic exposure, Po2 at all measurement sites had fallen very nearly in proportion to that in the inspired gas, but tissue oxygen levels did not reach critical Po2. Significant differences in oxyhemoglobin desaturation rate were also observed between arterial and microcirculatory vessels during hypoxia. In conclusion, the fall in microcirculatory and tissue oxygen levels in resting skeletal muscle is significantly slower than in arterial blood during a step reduction to an inspired oxygen fraction of 0.07, and tissue Po2 does not reach anaerobic levels.

ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1

2020 ◽  
Author(s):  
Huafeng Zhang ◽  
Tong Zhang ◽  
Linchong Sun ◽  
Yijie Hao ◽  
Wenhao Ma ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Rna Binding ◽  
Clinical Sample ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Aberrant Expression ◽  
Hcc Cells ◽  
Iron Regulatory Protein 1

Abstract α-Enolase 1 (ENO1) is a critical glycolytic enzyme whose aberrant expression drives the pathogenesis of various cancers. ENO1 has been indicated to have additional roles beyond its conventional metabolic activity, but the underlying mechanisms and biological consequences remain elusive. Here, we show that ENO1 suppresses iron regulatory protein 1 (IRP1) expression to regulate iron homeostasis and survival of hepatocellular carcinoma (HCC) cells. Mechanistically, we unprecedentedly uncover that ENO1, as an RNA-binding protein, recruits CNOT6 to accelerate the mRNA decay of IRP1 in cancer cells, leading to inhibition of mtioferin-1 (Mfrn1) expression and subsequent repression of mitochondrial iron-induced ferroptosis. Moreover, through in vitro and in vivo experiments and clinical sample analysis, we identified IRP1 and Mfrn1 as tumor suppressors by inducing ferroptosis in HCC cells. Taken together, this study establishes a novel role for the ENO1/IRP1/Mfrn1 pathway in the pathogenesis of HCC and reveals a previously unknown connection between the ENO1/IRP1/Mfrn1 pathway and ferroptosis, suggesting a potential innovative cancer therapy.

scholarly journals The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

2020 ◽  
Author(s):  
Enrico Castroflorio ◽  
Joery den Hoed ◽  
Daria Svistunova ◽  
Mattéa J. Finelli ◽  
Alberto Cebrian-Serrano ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Regulatory Protein ◽  
Molecular Function ◽  
Neuronal Connectivity ◽  
Nuclear Receptor Coactivator ◽  
Lysm Domain ◽  
Behavioural Assessment ◽  
And Function ◽  
The Brain

Abstract Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment. Graphic abstract

scholarly journals Continuous monitoring of interstitial tissue oxygen using subcutaneous oxygen microsensors: In vivo characterization in healthy volunteers

2019 ◽  
Vol 124 ◽  
pp. 6-18 ◽  
Author(s):  
Stephen C. Kanick ◽  
Peter A. Schneider ◽  
Bruce Klitzman ◽  
Natalie A. Wisniewski ◽  
Kerstin Rebrin
Keyword(s):  
Healthy Volunteers ◽  
Continuous Monitoring ◽  
Interstitial Tissue ◽  
Tissue Oxygen ◽  
In Vivo Characterization

scholarly journals Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Liping Huang ◽  
Yiyi Zhang ◽  
Yanan Li ◽  
Fanling Meng ◽  
Hongyu Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Near Infrared ◽  
Immune Escape ◽  
Regulatory Protein ◽  
In Vivo Studies ◽  
Breast Cancer Patients ◽  
Thermally Responsive ◽  
Immunosuppressive Microenvironment

AbstractThe highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.

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