Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc

1999 ◽  
Vol 17 (6) ◽  
pp. 829-835 ◽  
Author(s):  
Hirokazu Ishihara ◽  
Jill P. G. Urban
2019 ◽  
Author(s):  
Ulrik H. Pedroza-Dávila ◽  
Cristina Uribe-Alvarez ◽  
Lilia Morales-García ◽  
Emilio Espinoza-Simón ◽  
Adriana Muhlia-Almazán ◽  
...  

ABSTRACTStaphylococcus epidermidisis a Gram-positive saprophytic bacterium found in the microaerobic/anaerobic layers of the skin. It becomes a health hazard when introduced across the skin by punctures or wounds.S. epidermidisforms biofilms in low O2environments. As oxygen concentrations ([O2]) decreased, the metabolism ofS. epidermidiswas modified ranging from fully aerobic to anaerobic. Respiratory activity increased at high [O2], while anaerobically grown cells exhibited the highest rate of fermentation. High aerobic metabolism coincided with high hydrogen peroxide-mediated damage. Remarkably, the rate of growth decreased at low [O2] even though the concentration of ATP was high. Under these conditions bacteria associated into biofilms. Then, in the presence of metabolic inhibitors, biofilm formation decreased. It is suggested that when [O2] is lowS. epidermidisaccumulates ATP in order to synthesize the proteins and polysaccharides needed to attach to surfaces and form biofilms.ImportanceBacteria and humans coexist, establishing all kinds of relationships that may change from saprophytic to infectious as environmental conditions vary. S. epidermidis is saprophytic when living in the skin. Inside the organism it evokes a pathologic reaction and is thus rejected by the organism. Additionally it is forced to adapt to high oxygen concentrations, becoming vulnerable to reactive oxygen species, which may come from leukocyte attack. Avoiding both, high oxygen and leukocytes is a must for bacteria. Escaping from oxygen involves a clever response: whenever it finds a low oxygen environment it attaches to surfaces, associating into biofilms. Biofilms protectS. epidermidisagainst host cells. Understanding these responses is a must in order to develop treatments and prevent infection success.


Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 60
Author(s):  
Juan Vélez ◽  
Zahady Velasquez ◽  
Liliana M. R. Silva ◽  
Ulrich Gärtner ◽  
Klaus Failing ◽  
...  

Cryptosporidium parvum is an apicomplexan zoonotic parasite recognized as the second leading-cause of diarrhoea-induced mortality in children. In contrast to other apicomplexans, C.parvum has minimalistic metabolic capacities which are almost exclusively based on glycolysis. Consequently, C. parvum is highly dependent on its host cell metabolism. In vivo (within the intestine) infected epithelial host cells are typically exposed to low oxygen pressure (1–11% O2, termed physioxia). Here, we comparatively analyzed the metabolic signatures of C. parvum-infected HCT-8 cells cultured under both, hyperoxia (21% O2), representing the standard oxygen condition used in most experimental settings, and physioxia (5% O2), to be closer to the in vivo situation. The most pronounced effect of C. parvum infection on host cell metabolism was, on one side, an increase in glucose and glutamine uptake, and on the other side, an increase in lactate release. When cultured in a glutamine-deficient medium, C. parvum infection led to a massive increase in glucose consumption and lactate production. Together, these results point to the important role of both glycolysis and glutaminolysis during C. parvum intracellular replication. Referring to obtained metabolic signatures, we targeted glycolysis as well as glutaminolysis in C. parvum-infected host cells by using the inhibitors lonidamine [inhibitor of hexokinase, mitochondrial carrier protein (MCP) and monocarboxylate transporters (MCT) 1, 2, 4], galloflavin (lactate dehydrogenase inhibitor), syrosingopine (MCT1- and MCT4 inhibitor) and compound 968 (glutaminase inhibitor) under hyperoxic and physioxic conditions. In line with metabolic signatures, all inhibitors significantly reduced parasite replication under both oxygen conditions, thereby proving both energy-related metabolic pathways, glycolysis and glutaminolysis, but also lactate export mechanisms via MCTs as pivotal for C. parvum under in vivo physioxic conditions of mammals.


1992 ◽  
Vol 3 (5) ◽  
pp. 535-544 ◽  
Author(s):  
B C Gliniak ◽  
L S Park ◽  
L R Rohrschneider

The murine myeloid precursor cell line FDC-P1/MAC simultaneously expresses receptors for multi-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF. Growth of FDC-P1/MAC cells in either multi-CSF or GM-CSF results in the posttranscriptional suppression of M-CSF receptor (c-fms proto-oncogene) expression. We use the term transregulation to describe this control of receptor expression and have further characterized this regulatory process. The removal of FDC-P1/MAC cells from GM-CSF stimulation resulted in the re-expression of c-fms mRNA independent of M-CSF stimulation and new protein synthesis. Switching FDC-P1/MAC cells from growth in M-CSF to GM-CSF caused the selective degradation of c-fms mRNA within 6 h after factor switching. Blocking protein synthesis or gene transcription with metabolic inhibitors effectively prevented GM-CSF stimulated degradation of c-fms mRNA. These results suggest that the transregulation of c-fms transcripts by GM-CSF requires the transcriptional activation of a selective mRNA degradation factor. In vitro analysis, the use of cytoplasmic cell extracts, provided evidence that a ribonuclease is preferentially active in GM-CSF stimulated cells, although the specificity for mRNA degradation in vitro is broader than seen in vivo. Together, these data suggest that GM-CSF can dominantly transregulate the level of c-fms transcript through the transcriptional activation of a ribonuclease degradation system.


1939 ◽  
Vol 16 (3) ◽  
pp. 363-373 ◽  
Author(s):  
C. A. WINGFIELD

1. The oxygen consumption of normal and gill-less nymphs of the mayflies Baetis sp., Cloeon dipterum and Ephemera vulgata has been measured at various oxygen concentrations. 2. It has been found that over the complete range of oxygen concentrations studied, the tracheal gills do not aid oxygen consumption in Baetis sp. In Cloeon dipterum, at all oxygen concentrations tested, no gaseous exchange takes place through the gills; at low oxygen concentrations, however, the gills function as an accessory respiratory mechanism in ventilating the respiratory surface of the body and so aid oxygen consumption. In Ephemera Vulgata the gills aid oxygen consumption even at high oxygen concentrations. In this species the gills may function both as true respiratory organs and as a ventilating mechanism. 3. It is shown that the differences in gill function can be related to the oxygen content of the habitat of each species.


1996 ◽  
Vol 62 (7) ◽  
pp. 2427-2434 ◽  
Author(s):  
J Krooneman ◽  
E B Wieringa ◽  
E R Moore ◽  
J Gerritse ◽  
R A Prins ◽  
...  

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