Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria
Autor: | Matthew L. Turner, I. Martin Sheldon, Siân-Eleri Owens |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Glutamine Cell Membranes Cultured tumor cells Pathology and Laboratory Medicine Biochemistry chemistry.chemical_compound Hemolysin Proteins 0302 clinical medicine Mathematical and Statistical Techniques Animal Cells Medicine and Health Sciences Amino Acids Connective Tissue Cells 0303 health sciences Multidisciplinary Chemistry Cytotoxins Organic Compounds Acidic Amino Acids Statistics Neurochemistry Neurotransmitters Cytoprotection Lipids Cell biology Bacterial Pathogens Cholesterol Connective Tissue Medical Microbiology Streptolysins Physical Sciences Cell lines Medicine Streptolysin Cellular Types Anatomy Pathogens Glutamate Cellular Structures and Organelles Biological cultures Research Article Stromal cell Science Bacterial Toxins Microbiology 03 medical and health sciences Immune system Bacterial Proteins Lactate dehydrogenase Animals Humans Viability assay HeLa cells Statistical Methods Microbial Pathogens PI3K/AKT/mTOR pathway 030304 developmental biology Analysis of Variance Glutaminolysis L-Lactate Dehydrogenase Organic Chemistry Chemical Compounds Biology and Life Sciences Proteins Cell Biology Cell cultures Research and analysis methods 030104 developmental biology Biological Tissue Cattle Stromal Cells 030217 neurology & neurosurgery Mathematics Neuroscience |
Zdroj: | PLoS ONE, Vol 15, Iss 3, p e0219275 (2020) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine helped protect cells against cholesterol-dependent cytolysins because glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 ± 0.6 vs. 34.4 ± 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 ± 0.3 vs. 9.4 ± 1.0 AU). The cytoprotective effect of glutamine was not dependent on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria. |
Databáze: | OpenAIRE |
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