Chronic Microcystin-LR Exposure Induces Abnormal Lipid Metabolism via Endoplasmic Reticulum Stress in Male Zebrafish
Autor: | Liping Yang, Dapeng Li, Dandan Zhang, Lingkai Wang, Li Li, Yinjie Liu, Honghui Guo, Wang Lin, Rong Tang |
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Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Microcystins Health Toxicology and Mutagenesis lcsh:Medicine 010501 environmental sciences Toxicology 01 natural sciences Article 03 medical and health sciences Internal medicine medicine Animals RNA Messenger EIF2AK3 microcystin-LR zebrafish endoplasmic reticulum stress lipid metabolism Protein Unfolding 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences ACACA Dose-Response Relationship Drug biology Chemistry ATF6 Endoplasmic reticulum lcsh:R Lipid metabolism Zebrafish Proteins Endoplasmic Reticulum Stress Lipid Metabolism medicine.disease Fatty acid synthase Endocrinology Liver Unfolded protein response biology.protein Marine Toxins Steatosis Water Pollutants Chemical |
Zdroj: | Toxins; Volume 12; Issue 2; Pages: 107 Toxins Toxins, Vol 12, Iss 2, p 107 (2020) |
ISSN: | 2072-6651 |
Popis: | In order to explore effects of low levels of continuous microcystin-LR (MC-LR) (a cyanotoxin) exposure on hepatic lipid metabolism on the basis of the endoplasmic reticulum stress (ERS) pathway, we exposed adult male zebrafish to MC-LR (0, 1, 5, and 25 μg/L) for 60 days, and hepatic histopathology as well as lipid metabolic parameters were determined with mRNA levels of ERS signal molecules and downstream factors, along with genes associated with lipid metabolism in zebrafish liver. The results revealed that prolonged exposure to MC-LR remarkably altered the levels of hepatic total cholesterol and triglyceride and led to hepatic steatosis, which was also confirmed by hepatic cytoplasmic vacuolization in Hematoxylin/eosin (H&E) stain and lipid droplet accumulation in Oil Red O stain. The severity of hepatic damage and lipidation was increased in a dose-related manner. MC-LR exposure significantly upregulated transcriptional levels of ERS markers including hspa5, mapk8, and chop, indicating the occurrence of ERS in the liver of zebrafish. Concurrently, MC-LR significantly improved mRNA expression of unfolded protein response (UPR) pathway-related genes including atf6, eif2ak3, ern1, and xbp1s, suggesting that all of the three UPR branches were activated by MC-LR. MC-LR also induced significant upregulation of downstream lipid metabolism-related factors and genes including srebf1, srebf2, fatty acid synthase (fasn), acetyl-CoA carboxylase (acaca), stearoyl-CoA desaturase (scd), HMG CoA reductase (hmgcra), and HMG CoA synthase (hmgcs1), and downregulation of genes associated with lipolysis such as triglyceride hydrolase gene (atgl), hormone-sensitive enzyme gene (hsla), and carnitine palmitoyltransferase gene (cpt1aa). Our present results indicated that the cause of hepatic lipid accumulation by MC-LR was mainly by upregulating lipogenic and cholesterol genes but downregulating the expression of lipolytic genes through the induction of srebf1 and srebf2, which were involved in the activation of ERS signal pathways. |
Databáze: | OpenAIRE |
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