l-Serine protects mouse hippocampal neuronal HT22  cells against oxidative stress-mediated mitochondrial damage and apoptotic cell death.

l-Serine protects mouse hippocampal neuronal HT22 cells against oxidative stress-mediated mitochondrial damage and apoptotic cell death. Free Radic Biol Med. 2019 Jul 18;: Authors: Kim KY, Hwang SK, Park SY, Kim MJ, Jun DY, Kim YH Abstract The cytoprotective mechanism of l-serine against oxidative stress-mediated neuronal apoptosis was investigated in mouse hippocampal neuronal HT22 cells. Treatment with the reactive oxygen species (ROS) inducer 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) increased cytosolic and mitochondrial ROS and apoptosis, without necrosis, in HT22 cells. ROS-mediated apoptosis was accompanied by the induction of the endoplasmic reticulum (ER) stress-mediated apoptotic pathway, involving CHOP/GADD153 upregulation, JNK and p38 MAPK activation, and caspase-12 and caspase-8 activation, and subsequent induction of the mitochondrial apoptotic pathway through BAK and BAX activation, mitochondrial membrane potential (Δψm) loss, caspase-9 and caspase-3 activation, PARP cleavage, and nucleosomal DNA fragmentation. However, the DMNQ-caused ROS elevation and ER stress- and mitochondrial damage-induced apoptotic events were dose-dependently suppressed by co-treatment with l-serine (7.5-20 mM). Although DMNQ reduced both the intracellular glutathione (GSH) level and the ratios of reduced GSH to oxidized GSH (GSSG), the reduction was restored by co-treatment with l-serine. Co-treatment with GSH or N-acetylcysteine also ...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research