Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.

TNF-α-converting enzyme, a member of the ADAM (A disintegrin and metalloproteinase) protease family and also known as ADAM17, regulates inflammation and regeneration in health and disease. ADAM17 targets are involved in pain development and hypersensitivity in animal models of inflammatory and neuropathic pain. However, the role of ADAM17 in the pain pathway is largely unknown. Therefore, we used the hypomorphic ADAM17 (ADAM17ex/ex) mouse model to investigate the importance of ADAM17 in nociceptive behavior, morphology, and function of primary afferent nociceptors. ADAM17ex/ex mice were hyposensitive to noxious stimulation, showing elevated mechanical thresholds as well as impaired heat and cold sensitivity. Despite these differences, skin thickness and innervation were comparable to controls. Although dorsal root ganglia of ADAM17ex/ex mice exhibited normal morphology of peptidergic and nonpeptidergic neurons, a small but significant reduction in the number of isolectin ß-4-positive neurons was observed. Functional electrical properties of unmyelinated nociceptors showed differences in resting membrane potential, afterhyperpolarization, and firing patterns in specific subpopulations of sensory neurons in ADAM17ex/ex mice. However, spinal cord morphology and microglia activity in ADAM17ex/ex mice were not altered. Our data suggest that ADAM17 contributes to the processing of painful stimuli, with a complex mode of action orchestrating the function of neurons along the pain pathway.-Quarta, S., Mitric, M., Kalpachidou, T., Mair, N., Schiefermeier-Mach, N., Andratsch, M., Qi, Y., Langeslag, M., Malsch, P., Rose-John, S., Kress, M. Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.

Electrochemical behavior of pyrite in sulfuric acid in presence of amino acids belonging to the amino acid sequence of rusticyanin.

The impact of different concentrations of three amino acids (cysteine, histidine and methionine) which are part of the amino acid sequence of rusticyanin on dissolution of pyrite is investigated by the application of electrochemical techniques. Cyclic voltammetric studies conducted in the anodic direction from corrosion potential have shown that in the vicinity of corrosion potential, histidine and methionine do not influence dissolution of pyrite independently on their concentrations. On the other hand, cysteine and solutions of these amino acids in the molar ratios Cys:His:Met/1:1:1 and Cys:His:Met/1:2:1 accelerate dissolution at concentrations 10-2 mol L-1 and 10-3 mol L-1. Potentiodynamic polarization measurements showed that methionine does not affect the anodic and cathodic dissolution at all concentrations, while histidine does not affect significantly on the anodic dissolution at all concentrations. Cysteine and solutions of three amino acids in the molar ratio Cys:His:Met/1:1:1 and Cys:His:Met/1:2:1 cause intensive cathodic inhibition and anodic activation at concentrations 10-2 mol L-1 and 10-3 mol L-1 respectively.