Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions.
Marie-Laëtitia ThézénasBianca De LeoAlexis Laux-BiehlmannCemsel BafligilBernd ElgerThomas Theodor TapmeierKarl MortenNilufer RahmiogluStephanie G DakinPhilip D CharlesFernando Estrada MartinezGraham SteersOliver M FischerJoerg MuellerHolger Hess-StumppAndreas SteinmeyerSanjiv ManekKrina T ZondervanStephen KennedyChristian M BeckerCatherine ShangThomas M ZollnerBenedikt Mathias KesslerUdo OppermannPublished in: Scientific reports (2020)
Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.
Keyphrases
- oxidative stress
- reactive oxygen species
- dna damage
- diabetic rats
- cell death
- chronic pain
- neuropathic pain
- ischemia reperfusion injury
- induced apoptosis
- pain management
- polycystic ovary syndrome
- heat shock
- immune response
- escherichia coli
- small molecule
- type diabetes
- climate change
- staphylococcus aureus
- pregnant women
- high glucose
- protein protein
- endometrial cancer
- human health
- pregnancy outcomes
- red blood cell
- cell migration