MCFA alleviate H2 O2 -induced oxidative stress in AML12 cells via the ERK1/2/Nrf2 pathway.

Oxidative stress is an important factor in the occurrence and development of liver disease. Medium-chain fatty acids (MCFAs) have potential antioxidant function, whereas the exact underlying mechanism of MCFA in oxidative injury of hepatocytes remains unclear. In our present study, three different MCFAs, 8-carbon octanoic acid (OA), 10-carbon capric acid (CA), and 12-carbon lauric acid (LA), have been performed to observe their protective action for hepatocyte under the H2 O2 challenge. The result showed that MCFA treatment significantly increased the cell viability, T-AOC, and expression of antioxidant-related genes in AML12 cells under oxidative stress condition, and reduced reactive oxygen species (ROS) production. Moreover, MCFA treatment significantly increased the protein expression of Nrf2 and the phosphorylation level of ERK1/2; LA treatment significantly promoted the Nrf2 nuclear translocation. With a further test, the rescue ability of MCFA was blocked by treating with the ERK inhibitor U0126. Overall, our data suggested that MCFA treatment has positive impact on protecting AML12 cells against oxidative stress through ERK1/2/Nrf2 pathway.

Adipokine ZAG Alters Depression-Like Behavior by Regulating Oxidative Stress in Hippocampus.

Zinc-α2-glycoprotein (ZAG) is an adipokine involved in body metabolism, and now it has been shown to be present in the brain and play a role in some neurological diseases such as epilepsy and Alzheimer's disease. In the present study, we employed ZAG knockout (KO) mice to investigate the effects of ZAG on behaviors after fasting and in vitro used overexpression (OV) ZAG in HT-22 cells to further clarify the possibly underlying mechanism. The results showed that ZAG exists widely in the brain tissues of mice and significantly increased during fasting. In ZAG KO group the depression-like behaviors were significantly increased after fasting for 24 hours, meanwhile the hippocampal reactive oxygen species (ROS) content was significantly increased. In vitro, serum deprivation led to the increasing of neuronal death and ROS, the reduced mitochondrial membrane potential and ATP levels, while ZAG overexpression alleviated these negative effects. The ß3 adrenoreceptor (ß3AR)/protein kinase A (PKA)/cAMP response element-binding (CREB) pathway possibly mediated the effects of ZAG on antioxidation. These results proposed a possible target for novel therapeutic approaches to the treatment of depression and provide potential link between adipose tissue and psychiatric disease.