Repeated ethanol exposure influences key enzymes in cholesterol and lipid homeostasis via the AMPK pathway in the rat prefrontal cortex
Autor: | Ja Wook Koo, Ung Gu Kang, Shijie Xu, Gang Li, Se Jin Jeong |
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Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Health (social science) Prefrontal Cortex AMP-Activated Protein Kinases Reductase Toxicology Biochemistry Rats Sprague-Dawley 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Homeostasis Phosphorylation Protein kinase A Ethanol Chemistry Kinase Cholesterol AMPK Lipid metabolism General Medicine Lipid Metabolism Rats 030227 psychiatry Endocrinology Neurology Hydroxymethylglutaryl CoA Reductases 030217 neurology & neurosurgery Acetyl-CoA Carboxylase |
Zdroj: | Alcohol. 85:49-56 |
ISSN: | 0741-8329 |
Popis: | Cholesterol homeostasis has been proposed to be implicated in the development of addiction. However, the effects of ethanol on cholesterol homeostasis within the brain are not well understood. One of the most important regulators of cholesterol homeostasis is HMG-CoA reductase (HMG-CoAR), the rate-limiting enzyme of cholesterol biosynthesis. We examined the phosphorylation of HMG-CoAR and the other key regulator of lipid synthesis, acetyl-CoA carboxylase (ACC), following acute or chronic treatment with ethanol (0.5, 1, or 2 g/kg) in the rat prefrontal cortex. The phosphorylation of AMP-activated protein kinase (AMPK), which regulates the HMG-CoAR activity, and its well-known upstream regulators, was also studied. The phosphorylation of HMG-CoAR and ACC were transiently increased by ethanol treatment only in animals previously treated chronically with ethanol. Acute administration to naive animals did not induce the phosphorylation, regardless of dosage. Similarly, the phosphorylation of AMPK and the upstream regulators, LKB1 and CaMK4, were transiently increased only in chronically ethanol-treated animals. In naive animals, a high dose (2 g/kg) of ethanol decreased phosphorylation. The phosphorylation of TAK1, another upstream kinase of AMPK, was increased only from 30 min to 24 h after the chronic treatment with ethanol. Together, these results indicate that repeated exposure is required for the activating effect of ethanol on HMG-CoAR and ACC. This effect seems to be mediated by the AMPK system, and may contribute to the long-lasting neuroadaptation involved in the development of alcohol dependence. |
Databáze: | OpenAIRE |
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