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Article

Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1

1
Neuroscience Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
2
Lab of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(18), 3231; https://doi.org/10.3390/molecules24183231
Received: 8 August 2019 / Revised: 25 August 2019 / Accepted: 3 September 2019 / Published: 5 September 2019
(This article belongs to the Section Bioorganic Chemistry)
Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5′monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2. View Full-Text
Keywords: cyanate; HL-7702; Nrf2/ ho-1; ROS; lipid metabolism cyanate; HL-7702; Nrf2/ ho-1; ROS; lipid metabolism
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MDPI and ACS Style

Hu, L.; Tian, K.; Zhang, T.; Fan, C.-H.; Zhou, P.; Zeng, D.; Zhao, S.; Li, L.-S.; Smith, H.S.; Li, J.; Ran, J.-H. Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1. Molecules 2019, 24, 3231. https://doi.org/10.3390/molecules24183231

AMA Style

Hu L, Tian K, Zhang T, Fan C-H, Zhou P, Zeng D, Zhao S, Li L-S, Smith HS, Li J, Ran J-H. Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1. Molecules. 2019; 24(18):3231. https://doi.org/10.3390/molecules24183231

Chicago/Turabian Style

Hu, Ling, Kuan Tian, Tao Zhang, Chun-Hua Fan, Peng Zhou, Di Zeng, Shuang Zhao, Li-Sha Li, Hendrea S. Smith, Jing Li, and Jian-Hua Ran. 2019. "Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1" Molecules 24, no. 18: 3231. https://doi.org/10.3390/molecules24183231

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