scholarly journals Genetic Ablation of Calcium-independent Phospholipase A2γ Exacerbates Glomerular Injury in Adriamycin Nephrosis in Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hanan Elimam ◽  
Joan Papillon ◽  
Julie Guillemette ◽  
José R. Navarro-Betancourt ◽  
Andrey V. Cybulsky

Abstract Genetic ablation of calcium-independent phospholipase A2γ (iPLA2γ) in mice results in marked damage of mitochondria and enhanced autophagy in glomerular visceral epithelial cells (GECs) or podocytes. The present study addresses the role of iPLA2γ in glomerular injury. In adriamycin nephrosis, deletion of iPLA2γ exacerbated albuminuria and reduced podocyte number. Glomerular LC3-II increased and p62 decreased in adriamycin-treated iPLA2γ knockout (KO) mice, compared with treated control, in keeping with increased autophagy in KO. iPLA2γ KO GECs in culture also demonstrated increased autophagy, compared with control GECs. iPLA2γ KO GECs showed a reduced oxygen consumption rate and increased phosphorylation of AMP kinase (pAMPK), consistent with mitochondrial dysfunction. Adriamycin further stimulated pAMPK and autophagy. After co-transfection of GECs with mito-YFP (to label mitochondria) and RFP-LC3 (to label autophagosomes), or RFP-LAMP1 (to label lysosomes), there was greater colocalization of mito-YFP with RFP-LC3-II and with RFP-LAMP1 in iPLA2γ KO GECs, compared with WT, indicating enhanced mitophagy in KO. Adriamycin increased mitophagy in WT cells. Thus, iPLA2γ has a cytoprotective function in the normal glomerulus and in glomerulopathy, as deletion of iPLA2γ leads to mitochondrial damage and impaired energy homeostasis, as well as autophagy and mitophagy.

2005 ◽  
Vol 289 (6) ◽  
pp. H2673-H2679 ◽  
Author(s):  
Masahiro Shibata ◽  
Shigeru Ichioka ◽  
Akira Kamiya

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.


Toxins ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 266 ◽  
Author(s):  
Marlies Decleer ◽  
Jelena Jovanovic ◽  
Anita Vakula ◽  
Bozidar Udovicki ◽  
Rock-Seth Agoua ◽  
...  

2020 ◽  
Author(s):  
Chengyao Wang ◽  
Thao Dang ◽  
Jasmine Baste ◽  
Advait Anil Joshi ◽  
Abhinav Bhushan

AbstractThe intestinal environment is unique because it supports the intestinal epithelial cells under a normal oxygen environment and the microbiota under an anoxic environment. Due to importance of understanding the interactions between the epithelium and the microbiota, there is a strong need for developing representative and simple experimental models. Current approaches do not capture the dual-oxygen environment, require external anaerobic chambers, or are complex. Another major limitation is that in the solutions that can mimic the dual-oxygen environment, the oxygenation level of the epithelial cells is not known, raising the question whether the cells are hypoxic. We report standalone microfluidic devices that form a dual-oxygen environment without the use of an external anaerobic chamber or oxygen scavengers to coculture intestinal epithelial and bacterial cells. By changing the thickness of the device cover, the oxygen tension in the chamber could be modulated. We verified the oxygen levels using several tests: microscale oxygen sensitive sensors incorporated within the devices, hypoxic immunostaining of Caco-2 cells, and genetically encoded bacteria. Collectively, these methods monitored oxygen concentrations in devices more comprehensively than previous reports and allowed for control of oxygen tension to match the requirements of both intestinal cells and anaerobic bacteria. Our experimental model is supported by the mathematical model that considers diffusion of oxygen into the top chamber and the cellular oxygen consumption rate. This allowed us to experimentally determine the oxygen consumption rate of the epithelial cells more precisely.


1987 ◽  
pp. 263-268
Author(s):  
H. G. Preuss ◽  
J. Areas ◽  
P. Schubert ◽  
M. Lenhart ◽  
D. Slemmer

Author(s):  
Grażyna Mazurkiewicz-Boroń ◽  
Teresa Bednarz ◽  
Elżbieta Wilk-Woźniak

Microbial efficiency in a meromictic reservoirIndices of microbial efficiency (expressed as oxygen consumption and carbon dioxide release) were determined in the water column of the meromictic Piaseczno Reservoir (in an opencast sulphur mine), which is rich in sulphur compounds. Phytoplankton abundances were low in both the mixolimnion (up to 15 m depth) and monimolimnion (below 15 m depth). In summer and winter, carbon dioxide release was 3-fold and 5-fold higher, respectively, in the monimolimnion than in the mixolimnion. Laboratory enrichments of the sulphur substrate of the water resulted in a decrease in oxygen consumption rate of by about 42% in mixolimnion samples, and in the carbon dioxide release rate by about 69% in monimolimnion samples. Water temperature, pH and bivalent ion contents were of major importance in shaping the microbial metabolic efficiency in the mixolimnion, whilst in the monimolimnion these relationships were not evident.


2021 ◽  
Vol 22 (9) ◽  
pp. 4366
Author(s):  
Rebecca L. Paszkiewicz ◽  
Richard N. Bergman ◽  
Roberta S. Santos ◽  
Aaron P. Frank ◽  
Orison O. Woolcott ◽  
...  

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