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J.-O. Karlsson, S. Jonhede, A. Petersen, M. Zetterberg; Acute Effects of the Sigma-2 Receptor Agonist Siramesine on Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2432.
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Experiments were carried out to study the effects of siramesine on markers for apoptosis, oxidative damage and mitochondrial function in primary cultures of human lens epithelial cells (HLEC).
HLEC were incubated with 25 µM siramesine for 1, 2, 3, 4, 6 and 8 hours. Caspase-3 was assayed in cell extracts with DEVD-AMC. Mitochondrial depolarization was assayed with JC-1. Peroxide production was studied with DCF-DA and superoxide levels with hydroethidium. Glutathione levels were assayed with monochlorobimane.
Siramesine induced a significant increase of caspase-3 activity after 6h exposure to 25 µM siramesine. Nuclear morphology examined with Hoechst 33342 showed signs of apoptosis after the same time intervals. A significant increase in the production of peroxide and superoxide were found up to 4 -8 hours after administration of siramesine.
Siramesine, a piperidine analogue, was developed for the treatment of psychiatic disorders and is considered to be relatively nontoxic. This study, and others, indicate effects on cell growth, apoptosis and production of ROS. The sigma-2 receptor may be a regulator of HLEC growth and apoptosis.
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