Objectives: Fibromyalgia (FM) is a chronic pain condition of unclear etiology. We have analyzed, for the first time, the activity of a broad spectrum of aminopeptidases (APs) in patients with FM and controls to investigate whether they are involved in the pathophysiology of this syndrome.
Method: In this case-control study, we fluorometrically measured specific AP activities in serum samples of 75 patients with FM and 29 healthy controls. The predictive value of AP activities in FM was determined by receiver operating characteristic (ROC) analysis.
Results: Oxytocinase activity was higher in patients with FM than in controls ( < .001). A subgroup of patients with FM ( = 18; 24%) showed low levels of enkephalin-degrading aminopeptidase (EDA) activity when compared with the healthy controls ( < .001) and with the rest of FM patients ( < .001). There were no significant differences in the activity levels of aminopeptidase A, aminopeptidase B, aspartyl aminopeptidase, insulin-regulated aminopeptidase, pyroglutamyl aminopeptidase, or aminopeptidase N between FM patients and controls. According to ROC analysis, oxytocinase activity may be a good marker for differentiating individuals with FM from healthy subjects.
Conclusions: Our findings show that serum oxytocinase activity is increased in patients with FM, which could alter the metabolism of peptides with analgesic effects such as oxytocin and enkephalins. The determination of serum oxytocinase activity may aid in FM diagnosis. Additionally, we have identified a subpopulation of FM patients with abnormally low serum EDA activity.
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http://dx.doi.org/10.1177/1099800419854207 | DOI Listing |
Int J Mol Sci
November 2024
The Beijer Laboratory, Department of Pharmaceutical Biosciences, Neuropharmacology and Addiction Research, Biomedical Centre, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
The insulin-regulated aminopeptidase (IRAP; oxytocinase) is part of the M1 aminopeptidase family and is highly expressed in many tissues, including the neocortex and hippocampus of the brain. IRAP is involved in various physiological functions and has been identified as a receptor for the endogenous hexapeptide Angiotensin IV (Ang IV). The binding of Ang IV inhibits the enzymatic activity of IRAP and has been proven to enhance learning and memory in animal models.
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October 2024
Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Insulin-regulated aminopeptidase (IRAP) is an enzyme with important biological functions and the target of drug-discovery efforts. We combined in silico screening with a medicinal chemistry optimization campaign to discover a nanomolar inhibitor of IRAP based on a pyrazolylpyrimidine scaffold. This compound displays an excellent selectivity profile versus homologous aminopeptidases, and kinetic analysis suggests it utilizes an uncompetitive mechanism of action when inhibiting the cleavage of a typical dipeptidic substrate.
View Article and Find Full Text PDFPoult Sci
October 2024
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, PR China; Joint Nutrition Center for Animal Feeding of Sichuan University-Shengliyuan Group. Electronic address:
Myocyte enhancer factor 2A (MEF2A) is a transcription factor that plays a critical role in cell proliferation, differentiation and apoptosis. In contrast to the wide characterization of its regulation mechanism in mammalian skeletal muscle, its role in chickens is limited. Especially, its wide target genes remain to be identified.
View Article and Find Full Text PDFAutophagy
November 2024
The Key Laboratory for Chemical Biology of Fujian Province, State Key Laboratory for Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian Province, China.
Imaging of mitophagy is of significance as aberrant mitophagy is engaged in multiple diseases. Mitophagy has been imaged with synthetic or biotic pH sensors by reporting pH acidification en route delivery into lysosomes. To circumvent uncertainty of acidity-dependent signals, we herein report an nzyme-activatable probe ovalently ttached on itochondrial inner membrane (ECAM) for signal-persist mitophagy imaging.
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