Fig 5. Oleandrin is a potent yet toxic CG for the NKA-mediated reduction of PrP^C levels.

Comparison of (A) ouabain, a cardiotonic steroid sourced from the Strophanthus gratus plant native to eastern Africa, and (B) oleandrin, found in Nerium oleander, an ornamental shrub of uncertain origin. A lack of hydroxyl groups in the steroid core and the presence of additional methyl groups that are absent in ouabain account for the more hydrophobic characteristics of oleandrin. (C) Tenfold lower levels of oleandrin than ouabain cause a similar reduction in steady-state PrP^C levels during 7-day treatment of differentiated ReN VM cells. (D) Graphs comparing the means of western blot signal intensities of ATP1A1 and PrP^C levels and their standard deviations in 2 nM oleandrin- versus 20 nM ouabain-treated ReN VM cells. The number of asterisks shown reflect significance thresholds as follows: one: p<0.05; two: p<0.005; three: p<0.0005. (E) The potency of oleandrin translates to T98G cells and may reflect an ability of this CG to reduce not only levels of ATP1A1 but also ATP1A3. (F) Influence on cell viability (black squares), cellular ATP content (red triangles) and intracellular Ca²⁺ concentration ([Ca²⁺]_i, green circles) of 7-day exposure of ReN VM cells to a range of oleandrin concentrations (10 pM to 10 nM). Toxic concentrations of oleandrin (exceeding 3 nM) are shaded in grey.