Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway

Cheng, Xiangyang; Hu, Jing; Ya, Wang; Ye, Hongwei; Li, Xiaohong; Gao, Qin; Li, Zhenghong

doi:10.1155/2018/3071959

Cited by 48 publications

(51 citation statements)

References 42 publications

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“…In these cases, Dex used during and after the surgery likely makes some influence on the growth and invasion of glioma. 14,19 The present study showed an increase in phosphorylation levels of Akt, and ERK1/2 in glioma cells after exposure to Dex. Earlier research has shown that treatment with Dex is associated with an increase in [3H]thymidine incorporation into breast cancer cells and inhibition of cell death, suggesting that Dex stimulates proliferation.…”

Section: Discussionsupporting

confidence: 55%

“…Cell proliferation induced by Dex may be related to the observed activation of PI3K, Akt and ERK1/2, the signalling molecules downstream of α 2 -ARs. 14,19 The present study showed an increase in phosphorylation levels of Akt, and ERK1/2 in glioma cells after exposure to Dex. The effects of Dex on the proliferation of various tumour hence deserve attention.…”

Section: Discussionsupporting

confidence: 55%

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Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Yang

Chen

Yan

et al. 2019

J of Cellular Biochemistry

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With the extensive use of dexmedetomidine (Dex) in the surgical resection of tumours for its potent sedative and analgesic properties, its effects on various properties of tumours have received increased attention. The study described herein aimed to investigate the effects of Dex on glioma cells in the presence or absence of cisplatin (DDP). Glioma U251 and U87MG cells were treated with different doses (1‐50 nM) of Dex for 12 hours, then recultured in a Dex‐free medium. In addition, Dex was added to U251 and U87MG cells 12 hours before or simultaneously with a 12‐hour DDP treatment. Treatment with Dex increased the viability of both cell lines; this effect continued for at least 24 hours after Dex was removed. A cell invasion assay indicated that Dex inhibited cell invasion at 50 nM, but not at 10 nM. Western blot analysis showed that Dex increased the expression of phosphorylated extracellular‐signal‐regulated kinase 1/2, phosphoitide 3‐kinase and p‐AKT, but decreased ROCK protein levels at a dose of 50 nM. Intracellular Ca 2+ concentration was decreased by Dex in a dose‐dependent manner. DDP toxicity was attenuated by 10 nM Dex added either before or with DDP treatment. However, pretreatment with 50 nM Dex instead enhanced the toxicity of DDP. Single‐dose treatment with Dex did not significantly change glioma volume in nude mice, but changed the expression of Ki67 and matrix metalloproteinase‐3 in the tumour. In conclusion, this study provides evidence of the regulatory effects of Dex on proliferation, invasion and chemosensitivity of glioma cells, and outlines potential mechanisms for these effects.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 55%

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Yang

Chen

Yan

et al. 2019

J of Cellular Biochemistry

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“…Although data reveal no differences at this time that are consistent with I–R intolerance, exaggerated injury with T2D could involve differences pre‐ischaemia (influencing propensity to subsequent cell injury/death). There is evidence of changes in baseline Bcl2 proteins in models of T2D, differences that may be maintained or lost with I–R (Cheng et al., ). Findings are equivocal regarding baseline phospho‐AKT, including evidence of no change (Cheng et al., ; Desrois et al., ), reductions (Chen et al., ) or increases (Bouhidel et al., ; Cook et al., ) in T2D.…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence of changes in baseline Bcl2 proteins in models of T2D, differences that may be maintained or lost with I–R (Cheng et al., ). Findings are equivocal regarding baseline phospho‐AKT, including evidence of no change (Cheng et al., ; Desrois et al., ), reductions (Chen et al., ) or increases (Bouhidel et al., ; Cook et al., ) in T2D. Although post‐ischaemic AKT phosphorylation was unaltered by diabetes (Figure ), it is possible earlier inhibitory or stimulatory impacts of T2D may normalise by 45 min reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Chronic type 2 but not type 1 diabetes impairs myocardial ischaemic tolerance and preconditioning in C57Bl/6 mice

Russell

Griffith

Helman

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?What is the impact of chronic adult‐onset diabetes on cardiac ischaemic outcomes and preconditioning? What is the main finding and its importance?Chronic adult‐onset type 2 but not type 1 diabetes significantly impairs myocardial ischaemic tolerance and ischaemic preconditioning. Preconditioning may be detrimental in type 2 diabetes, exaggerating nitrosative stress and apoptotic protein expression. Abstract Effects of diabetes on myocardial responses to ischaemia–reperfusion (I–R) and cardioprotective stimuli remain contentious, potentially reflecting influences of disease duration and time of onset. Chronic adult‐onset type 1 diabetes (T1D) and type 2 diabetes (T2D) were modelled non‐genetically in male C57Bl/6 mice via 5 × 50 mg kg−1 daily streptozotocin (STZ) injections + 12 weeks’ standard chow or 1 × 75 mg kg−1 STZ injection + 12 weeks’ obesogenic diet (32% calories as fat, 57% carbohydrate, 11% protein), respectively. Systemic outcomes were assessed and myocardial responses to I–R ± ischaemic preconditioning (IPC; 3 × 5 min I–R) determined in Langendorff perfused hearts. Uncontrolled T1D was characterised by pronounced hyperglycaemia (25 mm fasting glucose), glucose intolerance and ∼10% body weight loss, whereas T2D mice exhibited moderate hyperglycaemia (15 mm), hyperinsulinaemia, glucose intolerance and 17% weight gain. Circulating ghrelin, resistin and noradrenaline were unchanged with T1D, while leptin increased and noradrenaline declined in T2D mice. Ischaemic tolerance and IPC were preserved in T1D hearts. In contrast, T2D worsened post‐ischaemic function (∼40% greater diastolic and contractile dysfunction) and cell death (100% higher troponin efflux), and abolished IPC protection. Whereas IPC reduced post‐ischaemic nitrotyrosine and pro‐apoptotic Bak and Bax levels in non‐diabetic hearts, these effects were reduced in T1D and IPC augmented Bax and nitrosylation in T2D hearts. The data demonstrate chronic T1D does not inhibit myocardial I–R tolerance or IPC, whereas metabolic and endocrine disruption in T2D is associated with ischaemic intolerance and inhibition of IPC. Indeed, normally protective IPC may exaggerate damage mechanisms in T2D hearts.

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“…Myocardial ischemia, characterized by a pathological condition, lacks blood supply to the heart . Myocardial ischemia/reperfusion (I/R), known to restore blood supply to ischemic area, causes further damage such as oxidative stress, arrhythmia, cell apoptosis, and cell death . Hypoxia/reoxygenation (H/R) is an important pathological process in the I/R phase of acute myocardial infarction .…”

Section: Introductionmentioning

confidence: 99%

MiR‐27 alleviates myocardial cell damage induced by hypoxia/reoxygenation via targeting TGFBR1 and inhibiting NF‐κB pathway

Zhang

2019

The Kaohsiung J of Med Scie

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MiR‐27 prevents atherosclerosis by inhibiting inflammatory responses induced by lipoprotein lipase. Overexpression of miR‐27b attenuates angiotensin‐induced atrial fibrosis. Nevertheless, studies have rarely investigated on the effect of miR‐27 in cardiomyocyte injury. H9c2 cells were transfected with miR‐27 mimic/inhibitor. Then the cell proliferation was tested by MTT assay and the cell apoptosis was detected by flow cytometry. The luciferase activity assay was utilized to analyze the relationship between miR‐27 and TGFBR1. Quantificational real‐time polymerase chain reaction and western blot were utilized to detect the cardiomyocyte differentiation marker and nuclear factor kappa B (NF‐κB) pathway. Our outcomes demonstrated that miR‐27 expression was downregulated cardiomyocyte injury subjected to hypoxia/reoxygenation (H/R). Additionally, overexpression of miR‐27 could significantly alleviate cardiomyocyte injury by regulating cell activity and apoptosis. The luciferase activity assay confirmed that transforming growth factor ß receptor 1 (TGFBR1) is a direct hallmark of miR‐27. Besides, overexpression of miR‐27 promoted the expression of TGFBR1 in H/R model. After transfection with miR‐27 mimic/inhibitor, the expression of NF‐κB pathway‐related proteins was decreased/increased. Taken together, our data manifested that miR‐27 repressed cardiomyocyte injury induced by H/R via mediating TGFBR1 and inhibiting NF‐κB signaling pathway. Furthermore, miR‐27/ TGFBR1 might be utilized as hopeful biomarkers for myocardial ischemia diagnosis and treatment.

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Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway

Cited by 48 publications

References 42 publications

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

Chronic type 2 but not type 1 diabetes impairs myocardial ischaemic tolerance and preconditioning in C57Bl/6 mice

MiR‐27 alleviates myocardial cell damage induced by hypoxia/reoxygenation via targeting TGFBR1 and inhibiting NF‐κB pathway

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