Isorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells. In addition, our studies revealed that ISO-mediated autophagy induction occurred in a SESN2 (sestrin 2)-dependent and BECN1 (Beclin 1, autophagy related)-independent manner. Furthermore, we identified that ISO treatment induced SESN2 expression via a MAPK8/JNK1 (mitogen-activated protein kinase 8)/JUN-dependent mechanism, in which ISO triggered MAPK8-dependent JUN activation and facilitated the binding of JUN to a consensus AP-1 binding site in the SESN2 promoter region, thereby led to a significant transcriptional induction of SESN2. Importantly, we found that SESN2 expression was dramatically downregulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues. Collectively, our results demonstrate that ISO treatment induces autophagy and inhibits bladder cancer growth through MAPK8-JUN-dependent transcriptional induction of SESN2, which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer.

Background: Nucleolin is a multifunctional protein, but nucleolin-SUMO is unexploited. Results: Nucleolin-SUMO at Lys-294 facilitated binding with mRNA substrate gadd45␣ by maintaining its nuclear localization during cellular response to arsenite exposure. Conclusion: Nucleolin-SUMO promoted arsenite-induced apoptosis by increasing GADD45␣ expression. Significance: We identified a new modification of nucleolin and its contribution to the functional paradigm of nucleolin in mRNA stability regulation.

Background Chronic kidney disease (CKD) has been considered as a major health problem in the world. Increasing uric acid (UA) could induce vascular endothelial injury, which is closely related to microinflammation, oxidative stress, and disorders of lipids metabolism. However, the specific mechanism that UA induces vascular endothelial cells injury in early CKD remains unknown. Methods Human umbilical vein endothelial cells (HUVECs) were cultured and subjected to different concentrations of UA for different periods. Early CKD rat model with elevated serum UA was established. Western blotting and quantitative real-time PCR (qPCR) were applied for measuring protein and mRNA expression of different cytokines. The animals were sacrificed and blood samples were collected for measurement of creatinine, UA, IL-1β, TNF-α, and ICAM-1. Renal tissues were pathologically examined by periodic acid-Schiff (PAS) or hematoxylin-eosin (HE) staining. Results The expression of IL-1β, ICAM-1, NLRP3 complexes, and activation of NLRP3 inflammasome could be induced by UA, but the changes induced by UA were partially reversed by siRNA NLRP3 or caspase 1 inhibitor. Furthermore, we identified that UA regulated the activation of NLRP3 inflammasome by activating ROS and K + efflux. In vivo results showed that UA caused the vascular endothelial injury by activating NLRP3/IL-1β pathway. While allopurinol could reduce UA level and may have protective effects on cardiovascular system. Conclusions UA could regulate NLRP3/IL-1β signaling pathway through ROS activation and K + efflux and further induce vascular endothelial cells injury in early stages of CKD.

SM22, a dominant protein in smooth muscle cells (SMCs), has been widely reported to be abnormally expressed in many solid tumors. However, the expression patterns of SM22 are not consistent in all tumors, not even in the same ones. Whether SM22 should be considered a tumor biomarker is still debated in different laboratories. Herein, we have carried out a systematical investigation to validate SM22 expression in the primary tissues of gastric cancer (GC). Of eight cases, seven samples were found in the elevated expression of SM22 proteins through proteomic analysis. The observation was further verified by the approaches of Western blotting and quantitative RT-PCR. Surprisingly, the results achieved from tissue microarray in 126 GC cases appeared contrary to the proteomic conclusion, in which the highly expressed SM22 was mainly found in smooth muscle layers, blood vessels, and myofibroblasts. This suggested that the increased abundance of SM22 in the cancerous regions was not caused by the presence of the GC cells. Furthermore, the expression of SM22 was measured in different GC cell lines and SMCs with Western blotting and quantitative RT-PCR. The results revealed that SM22 expression in SMCs was dramatically higher than that of the GC cells, which indicates that SM22 is unlikely to be a proper biomarker for GC. Instead, it can be considered a potential indicator for the abnormal developments of smooth muscles, blood vessels, or myofibroblasts triggered by tumorigenesis.