scholarly journals Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Mengling Wang ◽  
Feng Zeng ◽  
Fengling Ning ◽  
Yinhang Wang ◽  
Shilin Zhou ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Renal Fibrosis ◽  
Consumption Rate ◽  
Metabolic Reprogramming ◽  
Ceria Nanoparticles ◽  
Extracellular Acidification ◽  
Extracellular Acidification Rate

Abstract Background and aims Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases. The present study aims to determine whether CeNP-PEG has therapeutic value for renal fibrosis. Methods The unilateral ureteral obstructive fibrosis model was used to assess the therapeutic effects in vivo. Transforming growth factor beta1-induced epithelial-to-mesenchymal transition in HK-2 cells was used as the in vitro cell model. The seahorse bioscience X96 extracellular flux analyzer was used to measure the oxygen consumption rate and extracellular acidification rate. Results In the present study, CeNP-PEG treatment significantly ameliorated renal fibrosis by increased E-cadherin protein expression, and decreased α-SMA, Vimentin and Fibronectin expression both in vitro and in vivo. Additionally, CeNP-PEG significantly reduced the ROS formation and improved the levels of mitochondrial ATP. The seahorse analyzer assay demonstrated that the extracellular acidification rate markedly decreased, whereas the oxygen consumption rate markedly increased, in the presence of CeNP-PEG. Furthermore, the mitochondrial membrane potential markedly enhanced, hexokinase 1 and hexokinase 2 expression significantly decreased after treatment with CeNP-PEG. Conclusions CeNP-PEG can block the dysregulated metabolic status and exert protective function on renal fibrosis. This may provide another therapeutic option for renal fibrosis. Graphical Abstract

scholarly journals Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets

2021 ◽  
Vol 22 (16) ◽  
pp. 8367
Author(s):  
Hien Lau ◽  
Shiri Li ◽  
Nicole Corrales ◽  
Samuel Rodriguez ◽  
Mohammadreza Mohammadi ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Oxygen Consumption ◽  
Insulin Secretion ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
In Vitro Development ◽  
Porcine Islets ◽  
Vitro Development

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8–15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.

scholarly journals Evidence for a Physiological Mitochondrial Angiotensin II System in the Kidney Proximal Tubules

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 121-132
Author(s):  
Xiao Chun Li ◽  
Xinchun Zhou ◽  
Jia Long Zhuo
Keyword(s):  
Blood Pressure ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Physiological Role ◽  
Ang Ii ◽  
Extracellular Acidification ◽  
Extracellular Acidification Rate ◽  
Mitochondria Targeting

The present study tested the hypotheses that overexpression of an intracellular Ang II (angiotensin II) fusion protein, mito-ECFP/Ang II, selectively in the mitochondria of mouse proximal tubule cells induces mitochondrial oxidative and glycolytic responses and elevates blood pressure via the Ang II/AT 1a receptor/superoxide/NHE3 (the Na + /H + exchanger 3)-dependent mechanisms. A PT-selective, mitochondria-targeting adenoviral construct encoding Ad-sglt2-mito-ECFP/Ang II was used to test the hypotheses. The expression of mito-ECFP/Ang II was colocalized primarily with Mito-Tracker Red FM in mouse PT cells or with TMRM in kidney PTs. Mito-ECFP/Ang II markedly increased oxygen consumption rate as an index of mitochondrial oxidative response (69.5%; P <0.01) and extracellular acidification rate as an index of mitochondrial glycolytic response (34%; P <0.01). The mito-ECFP/Ang II–induced oxygen consumption rate and extracellular acidification rate responses were blocked by AT 1 blocker losartan ( P <0.01) and a mitochondria-targeting superoxide scavenger mito-TEMPO ( P <0.01). By contrast, the nonselective NO inhibitor L-NAME alone increased, whereas the mitochondria-targeting expression of AT 2 receptors (mito-AT 2 /GFP) attenuated the effects of mito-ECFP/Ang II ( P <0.01). In the kidney, overexpression of mito-ECFP/Ang II in the mitochondria of the PTs increased systolic blood pressure 12±3 mm Hg ( P <0.01), and the response was attenuated in PT-specific PT- Agtr1a −/− and PT- Nhe3 −/− mice ( P <0.01). Conversely, overexpression of AT 2 receptors selectively in the mitochondria of the PTs induced natriuretic responses in PT- Agtr1a −/− and PT- Nhe3 −/− mice ( P <0.01). Taken together, these results provide new evidence for a physiological role of PT mitochondrial Ang II/AT 1a /superoxide/NHE3 and Ang II/AT 2 /NO/NHE3 signaling pathways in maintaining blood pressure homeostasis.

scholarly journals Myricetin Exerts Anti-Obesity Effects through Upregulation of SIRT3 in Adipose Tissue

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1962 ◽  
Author(s):  
Seun Akindehin ◽  
Young-Suk Jung ◽  
Sang-Nam Kim ◽  
Yeon-Ho Son ◽  
Icksoo Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Biologically Active ◽  
Beneficial Effects ◽  
Reduced Body ◽  
Sirt3 Expression

Myricetin is a biologically active natural polyphenol with beneficial effects on metabolic health. This study aimed to examine the effects of myricetin on the expression levels of genes involved in lipolysis and mitochondrial respiration in adipocytes and the anti-obesity potential of myricetin. The results indicated that myricetin reduced triglyceride (TG) content and increased mitochondrial content and oxygen consumption rate (OCR) in adipocytes in vitro. To determine anti-obesity effect of myricetin, C57BL6/J mice were fed a high-fat diet (HFD) for eight weeks and then treated with myricetin (10 mg/kg) for 2 weeks. The in vivo treatment of myricetin reduced body weight by 11%. Furthermore, it improved the glucose tolerance, and increased fatty acid consumption of HFD-fed mice. Myricetin treatment increased Sirt3 expression and reduced the acetylation of mitochondrial proteins in adipose tissue. Finally, the knockdown of Sirt3 in adipocytes reduced the myricetin-induced increase in mitochondrial oxygen consumption rate by about 27% compared to controls. Our results indicated that myricetin exerted anti-obesity effects through the upregulation of Sirt3 expression and mitochondrial metabolism in adipose tissue.

THE IN VITRO ACTION OF ACTH ON THE OXYGEN CONSUMPTION OF SLICES OF CATTLE ADRENAL CORTEX

1953 ◽  
Vol 9 (4) ◽  
pp. 379-390 ◽  
Author(s):  
M. REISS ◽  
EVA BRUMMEL ◽  
I. D. K. HALKERSTON ◽  
F. E. BADRICK ◽  
M. FENWICK
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Linear Relationship ◽  
Adrenal Cortex ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Biological Assay ◽  
Percentage Increase ◽  
Small Doses

A technique for measuring the action of small doses of ACTH on the oxygen consumption of slices of cattle adrenal cortex is described. The oxygen consumption rate of such slices in vitro is increased by ACTH. A linear relationship between logarithm of the dose of ACTH and the percentage increase in the rate of oxygen uptake is obtained with this method, and its suitability for biological assay purposes has been investigated. The question of the specificity of this action of ACTH is discussed.

Abstract 484: Multimerization of BAFF Regulates B Cell Function and Growth of Aortic Aneurysms

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Vlad Serbulea ◽  
Philipp Jakobs ◽  
Srabani Sahu ◽  
Prasad Srikakulapu ◽  
Coleen A McNamara ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
B Cells ◽  
Angiotensin Ii ◽  
B Cell ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Plasma Cells ◽  
Aortic Aneurysms ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype

B cell activating factor (BAFF) regulates differentiation and survival of B cells by binding to the surface receptors BAFF receptor (BR3), transmembrane activator and CAML interactor (TACI) and B cell maturation antigen (BCMA). During differentiation, intracellular metabolic reprogramming is crucial, such as, naïve B cells are metabolically quiescent, whereas, antibody producing plasma cells are metabolically active. We have reported that depletion of B cells protects mice from abdominal aortic aneurysm (AA), however it is not clear how B cells promote AA growth. BAFF exists as a 3mer (binds only to BR3) or as a 60mer (binds to BR3, TACI and BCMA). Therefore, we hypothesize that BAFF multimerization regulates the immune and metabolic phenotype of B cells by binding to BAFF receptors and modulate AA growth. Immunohistology was performed on AA tissues collected from patients undergoing open AA repair. Experimental AA was induced by elastase perfusion of abdominal aorta or angiotensin II infusion (1000 ng/kg/min) method in 8 weeks old male C57BL/6 or apolipoprotein E knockout mice, respectively. Western blotting, flow cytometry and Seahorse extracellular flux assays were used to determine immune and metabolic changes in B cells in response to recombinant BAFF 3mer and 60mer. BR3+ B cells were detected in the milieu of BAFF in human AAs. Mouse AAs demonstrated significant infiltration (>50/section) of CD138+ plasma B cells, but few (4-10/section) CD20+ B cells. In vitro, BAFF 3mer induced canonical NF-kB, whereas, 60mer induced both canonical and non-canonical NF-kB signaling. Moreover, the 3mer significantly decreased mitochondrial density, oxygen consumption rate, and surface expression of IgD and IgM indicating a metabolically quiescent state of B cells. However, these parameters were significantly increased by the 60mer similar to plasma cells. Anti-BR3 IgG1, but not a control IgG1 antibody decreased BAFF 60mer-induced oxygen consumption rate by 50%. In a pilot study (n=10/group), anti-BR3 IgG1, but not the control IgG1 aggravated angiotensin II-induced AA growth. Altogether, our results suggest that BAFF 3mer and 60mer oppositely regulate immune and metabolic phenotype of B cells and inhibition of BAFF-BR3 signaling is detrimental for AA growth.

Development of a new oxygen consumption rate assay in cultures of Acanthamoeba (Protozoa: Lobosea) and its application to evaluate viability and amoebicidal activity in vitro

2015 ◽  
Vol 155 ◽  
pp. 35-39 ◽  
Author(s):  
I. Heredero-Bermejo ◽  
A. Criado-Fornelio ◽  
J. Soliveri ◽  
J.A. Díaz-Martín ◽  
J. Matilla-Fuentes ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Amoebicidal Activity

Nitric oxide modulates oxygen consumption by arteriolar walls in rat skeletal muscle

2005 ◽  
Vol 289 (6) ◽  
pp. H2673-H2679 ◽  
Author(s):  
Masahiro Shibata ◽  
Shigeru Ichioka ◽  
Akira Kamiya
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Phosphorescence Quenching ◽  
Arterial Blood ◽  
No Release ◽  
Vessel Walls

To study the role of nitric oxide (NO) in regulating oxygen consumption by vessel walls, the oxygen consumption rate of arteriolar walls in rat cremaster muscle was measured in vivo during flow-induced vasodilation and after inhibiting NO synthesis. The oxygen consumption rate of arteriolar walls was calculated based on the intra- and perivascular Po2 values measured by phosphorescence quenching laser microscopy. The perivascular Po2 value of the arterioles during vasodilation was significantly higher than under control conditions, although the intravascular Po2 values under both conditions were approximately the same. Inhibition of NO synthesis, on the other hand, caused a significant increase in arterial blood pressure and a significant decrease in arteriolar diameter. Inhibition of NO synthesis also caused a significant decrease in both the intra- and perivascular Po2 values of the arterioles. Inhibition of NO synthesis increased the oxygen consumption rate of the vessel walls by 42%, whereas enhancement of flow-induced NO release decreased it by 34%. These results suggest that NO plays an important role not only as a regulator of peripheral vascular tone but also as a modulator of tissue oxygenation by reducing oxygen consumption by vessel walls. In addition, enhancement of NO release during exercise may facilitate efficient oxygen supply to the surrounding high metabolic tissue.

scholarly journals Event-Associated Oxygen Consumption Rate Increases ca. Five-Fold When Interictal Activity Transforms into Seizure-Like Events In Vitro

2017 ◽  
Vol 18 (9) ◽  
pp. 1925 ◽  
Author(s):  
Karl Schoknecht ◽  
Nikolaus Berndt ◽  
Jörg Rösner ◽  
Uwe Heinemann ◽  
Jens Dreier ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate
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