Chiu PY, Luk KF, Leung HY, Ng KM, Ko KM
 Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
 Department of Chemical Engineering, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
The effects of the schisandrin B stereoisomers, (±)γ-schisandrin [(±)γ-Sch] and (−)schisandrin B [(−)Sch B], on hypoxia/reoxygenation-induced apoptosis were investigated in AML12 hepatocytes. Changes in cellular reduced glutathione (GSH) levels, Ca2+-induced mitochondrial permeability transitions (MPTs) and mitochondrial membrane potentials (Δψm values) were also examined in (±)γ-Sch- and (−)Sch B-treated cells, without or with hypoxia/reoxygenation challenge. The (±)γ-Sch/(−)Sch B pretreatments (2.5–5.0 µm) protected against hypoxia/reoxygenation-induced apoptosis in AML12 cells in a concentration-dependent manner, with the (−)Sch B effect being more potent. Drug antiapoptotic effects were further evidenced by suppression of hypoxia/reoxygenation-induced mitochondrial cytochrome c release and subsequent cleavage of caspase 3 and poly-ADP-ribose polymerase by (−)Sch B pretreatment. Whereas hypoxia/reoxygenation challenge increased the extent of Ca2+-induced MPT pore opening, and Δψm, in AML12 hepatocytes, cytoprotection afforded by (±)γ-Sch/(−)Sch B pretreatment against hypoxia/reoxygenation-induced apoptosis was associated with a decreased sensitivity to Ca2+-induced MPT and an increased Δψm in both unchallenged and challenged cells, compared with the drug-free control. The results indicate that (±)γ-Sch/(−)Sch B pretreatment protected against hypoxia/reoxygenation-induced apoptosis in AML12 hepatocytes and that the cytoprotection afforded by (±)γ-Sch/(−)Sch B may at least in part be mediated by a decrease in sensitivity to Ca2+-induced MPT, which may in turn result from enhancement of cellular GSH levels by drug pretreatments.