Suramin protects hepatocytes from LPS-induced apoptosis by regulating mitochondrial stress and inactivating the JNK-Mst1 signaling pathway
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An uncontrolled inflammatory response has been implicated in the progression of acute liver failure through poorly understood mechanisms. The aim of our study was to investigate whether suramin attenuates inflammation-mediated hepatocyte apoptosis by modulating mitochondrial homeostasis. Primary hepatocytes were isolated from mice and treated with LPS in vitro in the presence or absence of suramin. Western blotting, immunofluorescence staining, and ELISAs were used to evaluate the mitochondrial stress. The LPS treatment caused hepatocyte death via apoptosis. Interestingly, suramin supplementation attenuated LPS-mediated hepatocyte death by reducing Mst1 expression; the overexpression of Mst1 abolished the anti-apoptotic effects of suramin on LPS-treated hepatocytes. At the molecular level, suramin treatment repressed mitochondrial oxidative stress, sustained mitochondrial dynamics and blocked the caspase-9-mediated mitochondrial apoptosis pathway; these effects of suramin were achieved by reversing Mst1 expression. Furthermore, our study found that suramin modulated Mst1 expression via the JNK signaling pathway. Activation of JNK prevented the suramin-mediated Mst1 downregulation and concomitantly increased hepatocyte apoptosis and mitochondrial dysfunction. Taken together, our results confirmed the anti-apoptotic and anti-inflammatory effects of suramin on LPS-challenged hepatocytes. Suramin sustained hepatocyte viability and attenuated mitochondrial stress via repressing the JNK-Mst1 signaling pathway.
KeywordsSuramin Inflammation Mitochondria Hepatocyte death Mst1 JNK pathway
AZW, JLW, and JW made substantial contributions to the concept and design of the present study, XJD and YZ contributed to the performance of experiments, data analysis and interpretation, and manuscript writing.
This work was supported by Shanghai University of Medicine & Health Sciences Seed Project (SFP-18-22-14-011).
Compliance with ethical standards
Conflict of interests
The authors declare that they have no competing interests.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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