Cardiovascular PharmacologyCardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins
Introduction
There is growing recognition that the O-linked N-acetylglucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Numerous proteins have been identified as targets of O-GlcNAc modification including kinases, phosphatases, transcription factors and metabolic enzymes. Studies have shown that cells exposed to various stress stimuli exhibit elevated O-GlcNAc levels and this promotes cell survival (Yang et al., 2006, Zachara et al., 2004). It has recently been reported that preischemic treatment with glucosamine protects against ischemia and reperfusion injury in isolated rat hearts (Norbert et al., 2007) and this protection is associated with elevated levels of O-GlcNAc on nuclear and cytoplasmic proteins. The mechanisms underlying the cardioprotective effect associated with increased protein O-GlcNAc levels have yet to be determined. However, previous studies have shown that it may be mediated partly by changes in Ca2+ homeostasis (Liu et al., 2006, Nagy et al., 2006).
Rhodiola rosea is a popular medicinal plant found in mountains at high altitudes and has long been used in traditional Tibetan medicine system as an adaptogen to enhance the body's resistance to fatigue and to extend human life. Salidroside (p-hydroxyphenethyl-β-d-glucoside, chemical structure shown in Fig. 1), a major active ingredient isolated from the plant R. rosea, has been used in the treatment of diabetes, hypertension, fatigue and hypoxia (Kucinskaite et al., 2004, Wang et al., 2003). Recently, salidroside was reported to be capable of protecting SH-SY5Y cells against hydrogen peroxide-induced cell apoptosis in a dose-dependent manner (Zhang et al., 2007) and protecting the PC12 cells against hypoglycemia/serum limitation-induced cytotoxicity (Yu et al., 2008). Studies demonstrated that salidroside has protective effects on myocardial ischemia/reperfusion injury in isolated rat heart (Yan et al., 2008). However, the mechanisms have yet to be elucidated.
This study worked on protective effects of salidroside on cardiomyocyte ischemia/reperfusion injury. It was found that salidroside treatment attenuated ischemia/reperfusion injury, stimulated glucose uptake and elevated protein O-GlcNAc levels. Furthermore, alloxan, an inhibitor of O-GlcNAc transferase (OGT) (Konrad et al., 2002), markedly decreased the levels of O-GlcNAc and blocked the protection of salidroside.
Section snippets
Materials
Salidroside (purity 99%) was purchased from National Institute for the control of pharmaceutical and biological products (Beijing, China). Dulbecco's modified Eagle's medium (DMEM) was purchased from GIBCO (Auckland, NZ). Alloxan, Hoechst 33342 and [3H]-2-deoxyglucose were purchased from Sigma (St. Louis, MO, USA). Anti-O-GlcNAc antibody CTD110.6 was purchased from Covance (Princeton, NJ, USA). Fluo-3/acetoxymethyl ester (Fluo-3/AM) was purchased from CalbioChem (San Diego, CA, USA). 1- to
Salidroside prevented against ischemia/reperfusion-induced decrease in cell viability
Cardiomyocyte survival following ischemia/reperfusion was assessed by MTT assay (Fig. 2A). It was found that ischemia/reperfusion induced significant decrease in cell viability to 64.7 ± 4.5% as compared to control cells, while salidroside treatment resulted in a significant increase in cell survival, restoring cell survival to 85.8 ± 3.1% at the end of reperfusion. However, treatment with salidroside plus alloxan markedly decreased cell viability to 66.5 ± 3.8%. Our preliminary experiments showed
Discussion
Salidroside has been reported to have a wide range of pharmacological properties, including anti-inflammation, anti-hypoxia, anti-oxidative and hepatoprotective effects (Kanupriya et al., 2005, Kucinskaite et al., 2004). This study aimed to explore the protective effects of salidroside against ischemia/reperfusion injury in cardiomyocytes. In the present study, treatment of cardiomyocytes with salidroside significantly improved cell viability, decreased LDH release, attenuated cells apoptosis,
Acknowledgement
The authors are grateful to Dr. Xin L. Ma (Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, USA) for language editing.
References (27)
- et al.
Techniques for measuring and manipulating free Ca2+ in the cytosol and organelles of neutrophils
J. Immunol. Methods
(1999) - et al.
Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase
Biochem. Biophys. Res. Commun.
(2002) - et al.
Increased hexosamine biosynthesis and protein O-GlcNAc levels associated with myocardial protection against calcium paradox and ischemia
J. Mol. Cell. Cardiol.
(2006) Hexosamines as mediators of nutrient sensing and regulation in diabetes
J. Diabet. Its Complicat.
(2002)- et al.
Effect of salidroside on hemorheology and myocardial ischemic reperfusion injury in isolated heart of rats
Chin. J. Nat. Med.
(2008) - et al.
Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress. A survival response of mammalian cells
J. Biol. Chem.
(2004) - et al.
Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells
Eur. J. Pharmacol.
(2007) Protein kinase activation and myocardial ischemia/reperfusion injury
Cardiovasc. Res.
(2004)- et al.
Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway
J. Biol. Chem.
(2000) - et al.
Calcium, ATP, and ROS: a mitochondrial love–hate triangle
Am. J. Physiol., Cell. Physiol.
(2004)
New directions for protecting the heart against ischaemia–reperfusion injury: targeting the reperfusion injury salvage kinase (RISK)-pathway
Cardiovasc. Res.
Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the diabetic heart
Circ. Res.
Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages
Mol. Cell. Biochem.
Cited by (74)
Plant-microbial interaction: The mechanism and the application of microbial elicitor induced secondary metabolites biosynthesis in medicinal plants
2021, Plant Physiology and BiochemistryThe bioinformatics and metabolomics research on anti-hypoxic molecular mechanisms of Salidroside via regulating the PTEN mediated PI3K/Akt/NF-κB signaling pathway
2021, Chinese Journal of Natural MedicinesSalidroside: A review of its recent advances in synthetic pathways and pharmacological properties
2021, Chemico-Biological InteractionsCitation Excerpt :Salidroside has been examined and shown strong biological activity in numerous in vitro and in vivo studies of cells and animals. The main effects described so far are as follows: Activities on the cardiovascular system [20] and central nervous system [21–23], anti-hypoxia, anti-fatigue and anti-aging activities [24–26], anticancer activity [27], anti-inflammatory activity [28], antioxidant activity [29], antivirus and immune stimulation activities [30], antidiabetic activity [31], anti-osteoporotic activity [32]. These pharmacological properties suggest that salidroside may be a valuable therapeutic option for the prophylaxis and treatment of varieties of diseases, including atherosclerosis, Alzheimer's disease, Parkinson's disease, pneumonia, cardiovascular disease, etc.
Recent advances in chemistry and bioactivity of Sargentodoxa cuneata
2021, Journal of EthnopharmacologyHongjingtian injection protects against myocardial ischemia reperfusion-induced apoptosis by blocking ROS induced autophagic- flux
2021, Biomedicine and Pharmacotherapy
- 1
These authors contributed equally to this work.