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Oxidative Stress

Refers to increased levels of reactive oxygen species (ROS), mostly produced by cellular mitochondria. In non-immune cells, this was previously considered to be a defect and a by-product of oxidative metabolism, but it has now been proven to be part of the cellular stress-response where ROS acts as signal- and effector-molecules. ROS has been shown to mediate the cellular response to hypoxia, starvation, inflammation and infection and also regulates cellular autophagy and the process of autophagic cell-death. In general, increased levels of ROS corresponds to increased levels of cellular stress, and occurs at the expense of ATP-synthesis.

Figure showing the trigger and effect of mitochondrial ROS-production in a non-immunologic cell-type.

ROS-generation also creates a toxic intracellular environment and a general functional decline, but this is generally considered to be a necessary compromise to preserve cellular homeostasis in stressful conditions. In infection, up-regulated levels of ROS serves anti-microbial functions, especially in leukocytes where it is a prerequisite for efficient elimination of phagocytosed pathogens

Supporting Evidence

  • ROS-generation as an anti-microbial function, that might also get exploited by pathogens.1)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924804/
  • Signalling functions of ROS.2)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484374/
  • Increased production of ROS in mitochondria occurs at a compromise with ATP-synthesis.3)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605959/

Association with Disease

  • Increased levels of ROS in muscle of patients with MPS.4)https://www.ncbi.nlm.nih.gov/pubmed/23834645
  • Exposure of muscle-cells to ROS decreases force-generation capacity.5)https://www.physiology.org/doi/abs/10.1152/ajpcell.00272.2019
  • Evidence of redox-stress in joint-tissues from patients with OA and RA.6)https://www.sciencedirect.com/science/article/pii/S0925443916000041?via%3Dihub7)https://www.ncbi.nlm.nih.gov/pubmed/302367898)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051818/9)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064874/
  • Increased ROS-production by cells of the intervertebral disc in DDD.10)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368368/
  • A reduced capacity for ROS-synthesis by immune-cells might be involved in RA.11)https://www.ncbi.nlm.nih.gov/pubmed/19052348
  • Enhancement of leukocyte capacity for ROS-generation decreased arthritis in mouse-model.12)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564167/
  • Oxidative stress is a prominent feature in AS.13)https://www.ahajournals.org/doi/full/10.1161/01.cir.0000026393.47805.2114)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572357/

References   [ + ]

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