<p>Dynorphin A, dynorphin B and big dynorphin are endogenous opioid neuropeptides. They play an important role in a wide variety of physiological functions such as regulation of pain processing and memory acquisition. Such actions are generally mediated through the κ-receptors. Besides opioid receptor interactions, dynorphins have non-opioid physiological activities which result in excitotoxic effects in neuropathic pain, spinal cord and brain injury. In order to gain insight into the mechanisms of the non-opioid interactions of dynorphins with the cell, spectroscopic membrane-interaction studies were performed. We demonstrated that big dynorphin and dynorphin A, but not dynorphin B, penetrated into cells. All dynorphins interact with the membrane model systems with weak membrane-induced secondary structure. Big dynorphin and dynorphin A induce membrane perturbation, calcein leakage and cause permeability of the membrane to calcium in large unilamellar vesicles (LUV). But dynorphins do not translocate in the LUV membrane model system and there is a strong electrostatic contribution to the interaction of the peptides with the membrane bilayer.</p><p>In the second part of this thesis we investigated the amyloid β(1-40) peptide (Aβ). This peptide is related to Alzheimer’s disease and its soluble oligomeric aggregates are reported to contribute to the pathology of the disease. In order to provide better insight into the aggregation processes we examined the membrane interaction of Aβ in a model system. Gradual addition of small amounts of sodium dodecyl sulfate to an aqueous solution gives rise to a secondary structure conversion of Aβ peptide. The conversion can be described as a two state process, from random coil to β-sheet with formation of high molecular mass complexes between peptide and detergent, possibly mimicking the behavior of the peptide when aggregating at a cell membrane surface. At high detergent concentrations there is a transition from β-sheet to α-helix conformation.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:su-7156 |
| Date | January 2007 |
| Creators | Hugonin, Loïc |
| Publisher | Stockholm University, Department of Biochemistry and Biophysics, Stockholm : Institutionen för biokemi och biofysik |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
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