a-calcium-phosphate-induced-mouse-abdominal-aortic-aneurysm-model

A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease that occurs worldwide and is characterized by irreversible dilation of the ...

Chinese PLA general hospital

Chinese PLA General Hospital

Microcystin-LR (MC-LR) is a widely produced monocyclic heptapeptides in eutrophication waterbodies. MC-LR can induce various toxic effects in different cells. Our previous studies have found that MC-LR exposure can disrupt insulin signaling pathway in human liver cells (HL 7702). Skeletal muscle is one of the major organs for glucose disposal and responsive to insulin. However, the effects of MC-LR on insulin signaling pathway in muscle cells have not been fully explored. By using C2C12 mice muscle cells, this study aims to investigate the toxic effects of MC-LR in muscle cells with a focus on its effects on insulin signaling pathways. It was found that MC-LR entered into cells and inhibited protein phosphatase 2A (PP2A) significantly. Furthermore, MC-LR increased phosphorylation of Ser302, Ser307, Ser612 of insulin receptor substrate 1, AKT-Ser473, GSK3α-Ser21, and S6K1-Thr389 by inhibiting the activity of PP2A. The results in this study demonstrate that exposure of MCLR can disrupt the insulin pathway in muscle cells.

Microcystin-LR exposure disrupts the insulin signaling pathway in C2C12 mice muscle cell line.

Our previous work indicated exposure of Human liver cell 7702 (HL7702) cells to Microcystin-leucine-arginine (MC-LR) for 24 hours can disrupt insulin (INS) signaling by the hyperphosphorylation of specific proteins. For further exploring the time-dependent effect posed by MC-LR on this pathway, in the current study, HL7702 cells together with mice were exposed to the MC-LR with different concentrations under short-term treatment, and then, protein phosphatase 2A (PP2A) activity and expression of proteins related to INS signaling, as well as the characteristics of their action in the liver, were investigated. The results indicated, in HL7702 cells with 0.5, 1, and 6 hours of treatment by MC-LR, PP2A activity showed an obvious decrease in a time and concentration-dependent manner. While the total protein level of Akt, glycogen synthase kinase 3 (GSK-3), and glycogen synthase remained unchanged, GSK-3 and Akt phosphorylation increased significantly. In livers of mice with 1 hour of intraperitoneal injection with MC-LR, a similar change in these proteins was observed. In addition, the levels of total IRS1 and p-IRS1 at serine sites showed decreasing and increasing trends,respectively, and the hematoxylin and eosin staining showed that liver tissues of mice in the maximum-dose group exhibited obvious hepatocyte degeneration and hemorrhage. Our results further proved that short-term treatment with MC-LR can inhibit PP2A activity and disrupt INS signaling proteins' phosphorylation level, thereby interfering with the INS pathway. Our findings provide a helpful understanding of the toxic effects posed by MC-LR on the glucose metabolism of liver via interference with the INS signaling pathway.

Article	Year
Microcystin-LR exposure disrupts the insulin signaling pathway in C2C12 mice muscle cell line. Environmental toxicology\| PubMed ID: 31714646	2020
The effects of short-term treatment of microcystin-LR on the insulin pathway in both the HL7702 cell line and livers of mice. Environmental toxicology\| PubMed ID: 32073747	2020

Tianfeng Ma

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