High fat suppresses SOD1 activity by reducing copper chaperone for SOD1 associated with neurodegeneration and memory decline

Autor: Ping Lu, Cui Yang, Yue-Sheng Long, Hua-Juan Yan, Mei-Mei Gao, Wen-Cai Feng, Yue-Ying Wu, Fei Hu, Wei-Wen Sun
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
China
SOD1
Palmitic Acid
Diet
High-Fat
030226 pharmacology & pharmacy
General Biochemistry
Genetics and Molecular Biology
Cell Line
Palmitic acid
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Superoxide Dismutase-1
Memory
Internal medicine
medicine
Animals
General Pharmacology
Toxicology and Pharmaceutics
Cognitive decline
chemistry.chemical_classification
Reactive oxygen species
Memory Disorders
Chemistry
Superoxide Dismutase
Neurodegeneration
nutritional and metabolic diseases
Neurodegenerative Diseases
General Medicine
medicine.disease
Mitochondria
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
Enzyme
Cell culture
Saturated fatty acid
Reactive Oxygen Species
Copper
Molecular Chaperones
Zdroj: Life sciences. 272
ISSN: 1879-0631
Popis: 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.
Databáze: OpenAIRE
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