期刊
LIFE SCIENCES
卷 272, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119243
关键词
High fat; Cu/Zn superoxide dismutase (SOD1); Copper chaperone for SOD1 (CCS); Reactive oxygen species (ROS); Mitochondrial degeneration; Learning and memory
资金
- Guangzhou Science and Technology Program Key Projects [201804020046]
- National Natural Science Foundation of China [81671112]
- Innovative Academic Teams of Guangzhou Education System [1201610025]
The research suggests that high fat consumption leads to the generation of reactive oxygen species, decreases copper/zinc superoxide dismutase activity, and promotes neurodegeneration. Additionally, it was shown that saturated fatty acid palmitic acid decreases copper chaperone CCS levels, potentially leading to a decrease in SOD1 activity.
High fat consumption leads to reactive oxygen species (ROS) which is associated with age-progressive neurological disorders. Cu/Zn superoxide dismutase (SOD1) is a critical enzyme against ROS. However, the relationship between SOD1 and the high-fat-induced ROS and neurodegeneration is poorly known. Here we showed that, upon treatment with a saturated fatty acid palmitic acid (PA), the SOD1 activity was decreased in mouse neuronal HT-22 cell line accompanied by elevation of ROS, but not in mouse microglial BV-2 cell line. We further showed that PA decreased the levels of copper chaperone for SOD1 (CCS) in HT-22 cells, which promoted the nuclear import of SOD1 and decreased its activity. We demonstrated that the reduction of CCS is involved in the PA-induced decrease of SOD1 activity and elevation of ROS. In addition, compared with the adult mice fed with a standard diet, the high-fat-diet adult mice presented an increase of plasma free fatty acids, reduction of hippocampal SOD1 activity and CCS, mitochondrial degeneration and long-term memory decline. Taken together, our findings suggest that the high-fat-induced lower CCS level is essential for SOD1 suppression which may be associated with neurodegeneration and cognitive decline.
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