Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

Zhou, Yao; He, Weiming; Sun, Wei; Zhou, Zhanwei; Sun, Minjie; Xia, Peng; Li, Wei; Zheng, Min; Zhang, Lu; Ni, Jie; Gao, Kun

doi:10.1159/000489650

Cited by 9 publications

(10 citation statements)

References 29 publications

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“…Paraquat was used for inducing the production of ROS in tobacco. The ROS level was monitored using a ROS/Superoxide detection assay (Zhou et al, 2018 ). In this experiment, the ROS level induced by agrobacterium carrying an empty vector (i.e., no gene) plus PQ was normalized to 100%.…”

Section: Resultsmentioning

confidence: 99%

Two Liberibacter Proteins Combine to Suppress Critical Innate Immune Defenses in Citrus

et al. 2022

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We adopted a systems-based approach to determine the role of two Candidatus Liberibacter asiaticus (CLas) proteins, LasP235 and Effector 3, in Huanglongbing (HLB) pathogenesis. While a published work suggests the involvement of these CLas proteins HLB pathogenesis, the exact structure-based mechanism of their action has not been elucidated. We conducted the following experiments to determine the structure-based mechanisms of action. First, we immunoprecipitated the interacting citrus protein partners of LasP235 and Effector 3 from the healthy and CLas-infected Hamlin extracts and identified them by Liquid Chromatography with tandem mass spectrometry (LC–MS/MS). Second, we performed a split green fluorescent protein (GFP) assay in tobacco to validate that the interactions observed in vitro are also retained in planta. The notable in planta citrus targets of LasP235 and Effector 3 include citrus innate immune proteins. Third, in vitro and in planta studies were performed to show that LasP235 and Effector 3 interact with and inhibit the functions of multiple citrus proteins belonging to the innate immune pathways. These inhibitory interactions led to a high level of reactive oxygen species, blocking of bactericidal lipid transfer protein (LTP), and induction of premature programed cell death (PCD), all of which are beneficial to CLas lifecycle and HLB pathogenesis. Finally, we performed molecular dynamics simulations to visualize the interactions of LasP235 and Effector 3, respectively, with LTP and Kunitz protease inhibitor. This led to the design of an LTP mimic, which sequestered and blocked LasP235and rescued the bactericidal activity of LTP thereby proving that LasP235, indeed, participates in HLB pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Two Liberibacter Proteins Combine to Suppress Critical Innate Immune Defenses in Citrus

et al. 2022

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“…Further studies are merited to ascertain the safety and efficacy of Sal A therapy in preventing peritoneal fibrosis in patients undergoing peritoneal dialysis. Admittedly, S. miltiorrhiza also contains other active components, such as Tanshinone, which has been shown to be protective against peritoneal fibrosis ( 41 ). In addition, multiple other components of S. miltiorrhiza also have been shown to prevent peritoneal adhesions ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis

Zhou

Yao

et al. 2022

Front. Med.

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Peritoneal fibrosis is a devastating complication in patients undergoing peritoneal dialysis, with no definite therapy yet available. Salvia miltiorrhiza and its major active component Salvianolic acid A (Sal A) have demonstrated a beneficial effect in myriad diseases. However, their effect on peritoneal fibrosis is unknown. In murine models of peritoneal dialysis, daily Sal A treatment substantially improved the peritoneal dialysis fluid (PDF) elicited peritoneal fibrosis, marked by thickening of the submesothelial compact zone, accumulation of extracellular matrix and increased expression of vimentin and PAI-1, concomitant with attenuation of GSK3β hyperactivity. This coincided with diminished nitrotyrosine in peritoneal tissues and increased Nrf2 nuclear translocation, entailing a lessened oxidative injury and reinforced Nrf2 antioxidant response. Meanwhile, inflammatory infiltration and maladaptive angiogenesis in peritoneal tissues provoked by PDF injury were also mitigated by Sal A, associated with a suppressed NFκB activation. Mechanistically, ectopic expression of the constitutively active GSK3β blunted the NFκB-suppressing and Nrf2-activating efficacy of Sal A in peritoneal mesothelial cells exposed to hypertonic dextrose, suggesting that GSK3β inhibition mediates the protective effect of Sal A. Collectively, our findings may open the avenue for developing a novel therapy based on Sal A for preventing peritoneal fibrosis in peritoneal dialysis.

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“…ROS is a general term for oxygen-containing free radicals and peroxides that form free radicals related to oxygen metabolism in organisms, and its oxidizing properties are very active. ROS can cause membrane lipid peroxidation, protein cross-linking and degradation, DNA cleavage, and mitochondrial dysfunction of BMSCs [10]. Under physiological conditions, the body continuously produces reactive oxygen species, and the body's antioxidant system continuously scavenges the reactive oxygen species, which is in a state of dynamic equilibrium and will not cause harm to the body.…”

Section: Discussionmentioning

confidence: 99%

Effect of Oxidative Stress-Induced Autophagy on Proliferation and Apoptosis of hMSCs

Liu

Zheng

et al. 2022

Preprint

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Background:Objective:To observe the effect of H2O2 induced oxidative stress on autophagy and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs).Method: The hBMSCs were separated and cultured by density gradient centrifugation combined with adherence method. They were divided into blank group (with medium only), 3-MA (autophagy inhibitor) pretreatment group (with 2 ml of 5 mM 3-MA medium), H2O2 Intervention group (add 2ml medium containing 0.05mM H2O2), H2O2+3-MA treatment group (add 2ml medium containing 5mM 3-MA, then add 2ml medium containing 0.05mM H2O2). DCFH-DA staining was used to detect cellular reactive oxygen species (ROS) levels,and CCK-8 analysis was used to detect the effects of different concentrations (0,50,100,200,400μmol/L) of H2O2 on the proliferation of hBMSCs; Monodansylcadaverine(MDC) Fluorescent amine probe staining, Lysosome Red Fluorescent Probe (Lyso-Tracker Red) staining to observe the level of autophagy; Immunofluorescence staining to detect the expression of LC3A/B; Flow cytometry (Annexin V/PI) to detect cell apoptosis Circumstances; Protein chip detection of autophagy-related proteins; Western blot detection of Beclin1, mTOR, p-mTOR, LC3A/B, and Cleaved caspase-3 protein expression.Result: After treating hBMSCs with different concentrations of H2O2 (0,50,100,200,400μmol) for 24h ,48h, and 72h, with the increase of H2O2 concentration, the cell proliferation ability decreased; while with the extension of time, the cell proliferation ability increased not significantly; 50μmol cell proliferation ability is the strongest. Compared with the blank group and 3-MA group, the H2O2 intervention group increased the level of intracellular ROS, increased autophagosomes, and significantly decreased the apoptosis rate; up-regulated Beclin1, mTOR, LC3A/B and Cleaved caspase-3 protein expression, and down-regulated p-mTOR Protein expression level. Compared with the autophagy inhibitor 3-MA group, the H2O2+3-MA group increased the level of intracellular ROS, increased autophagosomes, and did not significantly increase the apoptosis rate; up-regulated the protein expression of Beclin1, mTOR, LC3A/B and Cleaved caspase-3 Down-regulate the expression of p-mTOR protein.Conclusion: H2O2 can induce hMSCs to produce oxidative stress response. Under oxidative stress conditions, hMSCs can promote protective autophagy and reduce cell apoptosis or the level of apoptosis caused by excessive autophagy.

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Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

Cited by 9 publications

References 29 publications

Two Liberibacter Proteins Combine to Suppress Critical Innate Immune Defenses in Citrus

Two Liberibacter Proteins Combine to Suppress Critical Innate Immune Defenses in Citrus

Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis

Effect of Oxidative Stress-Induced Autophagy on Proliferation and Apoptosis of hMSCs

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