g., 3,3′,4′,5-trans-tetrahydroxystilbene (piceatannol), 3,3′,5,5′-trans-tetrahydroxystilbene (3,3′,5,5′-THS) and 3,3′,4′,5,5′-trans-pentahydroxystilbene (3,3′,4′,5,5′-PHS). All these compounds were cytotoxic Prexasertib to growth-arrested C6 cells, with EC(50)-values between 20 and 85 mu M. A higher cytotoxic potency in proliferating cells indicated a specific cytostatic activity of resveratrol and 3,3′,4′,5,5′-PHS. All hydroxystilbenes studied inhibited cellular radical generation induced by cumene hydroperoxide (CH P). The rank order of antioxidant potency was resveratrol >

piceatannol > 3,3′,5,5′-THS>3,3′,4′,5,5′-PHS. However, only resveratrol and piceatannol inhibited cellular radical generation at lower than cytotoxic concentrations. At subcytotoxic concentrations only piceatannol was able to protect the cells from damage caused by CHP. Taken together, these results show that neither the cytotoxic or cytostatic activities of hydroxystilbenes nor their cytoprotective

and antioxidant activities in living cells can be predicted from their antioxidant and prooxidant activity, respectively, in cell-free systems. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“In Alzheimer disease (AD), the perturbation of the endoplasmic reticulum (ER) calcium (Ca2+) homeostasis has been linked to presenilins, the catalytic core in gamma-secretase complexes CH5183284 cleaving

the amyloid precursor protein (APP), thereby generating amyloid-beta (A beta) peptides. Here we investigate whether APP contributes to ER Ca2+ homeostasis and whether ER Ca2+ could in turn influence A beta production. We show that overexpression of wild-type human APP (APP(695)), or APP harboring the Swedish Galunisertib supplier double mutation (APP(swe)) triggers increased ryanodine receptor (RyR) expression and enhances RyR-mediated ER Ca2+ release in SH-SY5Y neuroblastoma cells and in APPswe-expressing (Tg2576) mice. Interestingly, dantrolene-induced lowering of RyR-mediated Ca2+ release leads to the reduction of both intracellular and extracellular A beta load in neuroblastoma cells as well as in primary cultured neurons derived from Tg2576 mice. This A beta reduction can be accounted for by decreased Thr-668-dependent APP phosphorylation and beta- and gamma-secretases activities. Importantly, dantrolene diminishes A beta load, reduces A beta-related histological lesions, and slows down learning and memory deficits in Tg2576 mice. Overall, our data document a key role of RyR in A beta production and learning and memory performances, and delineate RyR-mediated control of Ca2+ homeostasis as a physiological paradigm that could be targeted for innovative therapeutic approaches.