Lipopolysaccharide exposure induces oxidative damage in Caenorhabditis elegans: protective effects of carnosine release_zoqxsfzaqbfubhgiiv2otgv4my

by Jing Ma, Xiaoyuan Xu, Ranran Wang, Haijing Yan, Huijuan Yao, Hongmei Zhang, Shaowei Jiang, Ajing Xu

Published in BMC Pharmacology and Toxicology by Springer Science and Business Media LLC.

2020   Volume 21, Issue 1, p85

Abstract

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in <jats:italic>Caenorhabditis elegans</jats:italic>. </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:italic>C. elegans</jats:italic> individuals were stimulated for 24 h with LPS (100 μg/mL), with or without carnosine (0.1, 1, 10 mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of <jats:italic>sod-1</jats:italic>, <jats:italic>sod-2</jats:italic>, <jats:italic>sod-3</jats:italic>, <jats:italic>daf-16</jats:italic>, <jats:italic>ced-3</jats:italic>, <jats:italic>ced-9</jats:italic>, <jats:italic>sek-1</jats:italic>, and <jats:italic>pmk-1</jats:italic>. Western blotting was used to determine the levels of SEK1, p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. <jats:italic>C. elegans sek-1</jats:italic> (km2) mutants and <jats:italic>pmk-1</jats:italic> (km25) mutants were used to elucidate the role of the p38 MAPK signaling pathway. </jats:sec><jats:sec> <jats:title>Results</jats:title> Carnosine improved the survival of LPS-treated <jats:italic>C. elegans</jats:italic> and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type <jats:italic>C. elegans</jats:italic> up-regulated the mRNA expression of the antioxidant-related genes <jats:italic>sod-1</jats:italic>, <jats:italic>sod-2</jats:italic>, <jats:italic>sod-3</jats:italic>, and <jats:italic>daf-16</jats:italic>. The expression of the anti-apoptosis-related gene <jats:italic>ced-9</jats:italic> and apoptosis-related gene <jats:italic>ced-3</jats:italic> was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated <jats:italic>C. elegans</jats:italic>. Apoptosis in the loss-of-function strains of the p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the <jats:italic>sek-1</jats:italic> and <jats:italic>pmk-1</jats:italic> mutants. The expression levels of <jats:italic>sek-1</jats:italic> and <jats:italic>pmk-1</jats:italic> mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine. </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the p38 MAPK pathway. </jats:sec>
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