Dataset Information

Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways.

ABSTRACT:

Background

Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases.

Objective

We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro.

Methods

H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (± dP/dt max/min).

Results

NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P-PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardiac dysfunction.

Conclusion

We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1.

SUBMITTER: Yu Y

PROVIDER: S-EPMC4757886 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways.

Yu Yingli Y Sun Guibo G Luo Yun Y Wang Min M Chen Rongchang R Zhang Jingyi J Ai Qidi Q Xing Na N Sun Xiaobo X

Scientific reports 20160218

<h4>Background</h4>Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases.<h4>Objective</h4>We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro.<h4>Methods</h4>H9c2 cad ...[more]

PMID: 26888485

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Project description:The functional status of mitochondria and the endoplasmic reticulum are central to renal ischemia/reperfusion injury (IRI). X-box binding protein 1 (XBP1) is an important transcription factor in endoplasmic reticulum stress. NLR family pyrin domain containing-3 (NLRP3) inflammatory bodies are closely related to renal IRI. In vivo and in vitro, we examined the molecular mechanisms and functions of XBP1-NLRP3 signaling in renal IRI, which influences ER-mitochondrial crosstalk. In this study, mice were subjected to 45 min of unilateral renal warm ischemia, the other kidney resected, and reperfusion was performed for 24 h in vivo. In vitro, murine renal tubular epithelial cells (TCMK-1) were exposed to hypoxia for 24 h and reoxygenation for 2 h. Tissue or cell damage was evaluated by measuring blood urea nitrogen and creatinine levels, histological staining, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick-end labeling, diethylene glycol staining, and transmission electron microscopy (TEM). Western blotting, immunofluorescence staining, and ELISA were used to analyze protein expression. Whether XBP1 regulates the NLRP3 promoter was evaluated using a luciferase reporter assay. Kidney damage was reduced with decreasing blood urea nitrogen, creatinine, interleukin-1β, and interleukin-18 levels. XBP1 deficiency reduced tissue damage and cell apoptosis, protecting the mitochondria. Disruption of XBP1 was associated with reduced NLRP3 and cleaved caspase-1 levels and markedly improved survival. In vitro in TCMK-1 cells, XBP1 interference inhibited caspase-1-dependent mitochondrial damage and reduced the production of mitochondrial reactive oxygen species. The luciferase assay showed that spliced XBP1 isoforms enhanced the activity of the NLRP3 promoter. These findings reveal that XBP1 downregulation suppresses the expression of NLRP3, a potential regulator of endoplasmic reticulum mitochondrial crosstalk in nephritic injury and a potential therapeutic target in XBP1-mediated aseptic nephritis.

Dataset Information

Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways.

Background

Objective

Methods

Results

Conclusion

Publications

Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways.

Similar Datasets

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