Olfactory ensheathing cell-conditioned medium reverts 3 Ab25–35-induced oxidative damage in SH-SY5Y cells 4 by modulating the mitochondria-mediated apoptotic pathway.

Abstract

Olfactory ensheathing cells (OECs) are a type of 10 glia from the mammalian olfactory system, with neuro- 11 protective and regenerative properties. b-Amyloid peptides 12 are a major component of the senile plaques characteristic 13 of the Alzheimer brain. The amyloid beta (Ab) precursor 14 protein is cleaved to amyloid peptides, and Ab25–35 is 15 regarded to be the functional domain of Ab, responsible for 16 its neurotoxic properties. It has been reported that Ab25–35 17 triggers reactive oxygen species (ROS)-mediated oxidative 18 damage, altering the structure and function of mitochon- 19 dria, leading to the activation of the mitochondrial intrinsic 20 apoptotic pathway. Our goal is to investigate the effects of 21 OECs on the toxicity of aggregated Ab25–35, in human 22 neuroblastoma SH-SY5Y cells. For such purpose, SH- 23 SY5Y cells were incubated with Ab25–35 and OEC-conditioned medium (OECCM). OECCM promoted the 24 cell viability and reduced the apoptosis, and decreased the 25 intracellular ROS and the lipid peroxidation. In the pres- 26 ence of OECCM, mRNA and protein levels of antioxidant 27 enzymes (SOD1 and SOD2) were upregulated. Concomi- 28 tantly, OECCM decreased mRNA and the protein expres- 29 sion levels of cytochrome c, caspase-9, caspase-3, and Bax 30 in SH-SY5Y cells, and increased mRNA and the protein 31 expression level of Bcl-2. However, OECCM did not alter 32 intracellular Ca 33 2? concentration in SH-SY5Y cells. Taken together, our data suggest that OECCM ameliorates 34 Ab25–35-induced oxidative damage in neuroblastoma SH- 35 SY5Y cells by inhibiting the mitochondrial intrinsic path- 36 way. These data provide new insights into the functional 37 actions of OECCM on oxidative stress-induced cell 38 damage.