[Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells].
Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)-deprenyl has been shown in a number of different diseases, such as Parkinson's and Alzheimer's disease, atherosclerosis or tumor formation. The role of the cytoskeleton, the main component of cell adhesion, has been suggested in the development of these diseases. Nevertheless, the effect of the drug on cell adhesion has never been examined. In the present study, the authors studied the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase-B, and we observed the same effect in NIH3T3 cells at concentrations lower than those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. At the same time, the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell-cell adhesion both in neuronal and non neuronal cells. The authors' results with S-(+)-deprenyl suggest that the sterical structure of the drug is an important factor of the observed effect, which is probably a consequence of an irreversible change in the cells.
Jenei
Veronika
V
Magyar Tudományos Akadémia, Kémiai Kutatóközpont, Biomolekuláris Kémiai Intézet, Budapest. veronika@chemres.hu
Zor
Kinga
K
Magyar
Kálmán
K
Jakus
Judit
J
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D066246:ErbB Receptors