Effect of panaxydol on hypoxia-induced cell death and expression and secretion of neurotrophic factors (NTFs) in hypoxic primary cultured Schwann cells

It has been shown that panaxydol (PND) can mimic the neurotrophic effect of nerve growth factor (NGF) normally secreted by Schwann cells (SC) and protect neurons against injury. To evaluate the effect of PND on hypoxia-induced SC death and expression and secretion of neurotrophic factors (NGF and brain derived neurotrophic factor (BDNF)), hypoxic SCS were cultured in vitro and then treated with PND (0-20 mu M). The MTT (3(4,5-dimethylthiazol-2yl)2,5-diphenyltetrazolium bromide) assay, immunocytochemistry, ELISA and RT-PCR were employed to examine the effects. We found that hypoxia resulted in a significant decrease in SCs viability (MTT: 64 +/- 4.7% of control group) and nearly a 3.3-fold increase of intracellular level of active caspase-3. PND (5-20 mu M) treatment significantly rescued the SCs from hypoxia-induced injury (85 +/- 8.2%; 92 +/- 8.6%; 87 +/- 7.3%) and reduced caspase-3 activity with the maximal effect occurred at 10 mu M (P < 0.01), reducing to about 1.6-fold of control level. Furthermore, PND treatment also enhanced NGF and BDNF mRNA levels in hypoxic SCs and promoted protein expression and secretion. BDNF mRNA in hypoxic SCs was restored to about 90% of normal level and NGF mRNA was elevated to 1.4-fold of control after 10 PM PND treatment. These observations showed that PND protects primary cultured SCs against hypoxia-induced injury and enhances NTF-associated activities. (c) 2008 Elsevier Ireland Ltd. All rights reserved.