Dexmedetomidine protects against oxygen-glucose deprivation/reoxygenation injury-induced apoptosis via the p38 MAPK/ERK signalling pathway

Wang, Ke; Zhu, Yuekun

doi:10.1177/0300060517734460

Cited by 26 publications

(18 citation statements)

References 32 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, Bonney EA t et al 52 reported attenuated ischaemia-reperfusion injury mediated by inhibition of the p38MAPK signalling pathway. Wang et al 28 also illustrated the effect of DEX in altering oxygen deprivation/reoxygenation-induced apoptosis via the p38MAPK signalling pathway in N2A cells. In this study, Figure 7 The effects of dexmedetomidine on the expression of GRP78, CHOP and caspase-12 in myocardial cells treated under different conditions were evaluated.…”

Section: Discussionmentioning

confidence: 99%

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

Zhu

Ling

Zhou

et al. 2020

DDDT

View full text Add to dashboard Cite

Background: Myocardial ischaemia-reperfusion injury (IRI) has been confirmed to induce endoplasmic reticulum stress (ERS) when myocardial cell function continues to deteriorate to a certain degree. The clinical applications of effective tested strategies are sometimes inconsistent with the applications evaluated in experiments, although reasonable mechanisms and diverse signalling pathways have been broadly explored. Dexmedetomidine (DEX) has been shown to attenuate IRI of the heart in animal studies. This study aimed to determine whether DEX can protect injured cardiomyocytes under hypoxia/reoxygenation (H/R) at the cellular level and whether the mechanism is related to ERS and the p38 MAPK pathway. Methods: H9c2 cells were subjected to H/R or thapsigargin (TG) to build a model. DEX or 4-PBA was added to the medium either 1 h or 24 h before modelling, respectively. Model parameters were determined by assessing cell viability and injury, which were measured by assessing cell counting kit-8 (CCK8), lactate dehydrogenase (LDH) release and flow cytometry results, and the expression of GRP78, CHOP and caspase-12. In addition, the protein expression of p38MAPK and p-p38MAPK was examined, and SB202190, a negative regulator, was also preincubated in medium. Results: Compared to that of cells in the control group, the activity of cells in the H/R and TG groups was decreased dramatically, and the LDH concentration and proportion of apoptotic cells were increased. DEX could correspondingly reverse the changes induced by H/R or TG. Additionally, DEX effectively attenuated ERS defined as increased expression of GRP78, CHOP and caspase-12. Additionally, DEX could obviously depress the P38 MAPK phosphorylation and high p-p38 MAPK expression in the TG group, indicating DEX has a function similar to that of SB202190. Conclusion: H/R injury in H9c2 cells can lead to abnormal ERS and apoptosis, as well as activation of the p38MAPK signalling pathway. DEX can protect cardiomyocytes by intervening in ERS, regulating p38MAPK and the downstream apoptotic signalling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

Zhu

Ling

Zhou

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“…Recent studies showed that DEX has a protective effect on kidney injury [ 29 ]. In addition, DEX has been shown to inhibit the release of proinflammatory cytokines [ 30 , 31 ], attenuate apoptosis [ 32 , 33 ], and reduce ROS production [ 34 , 35 ]. However, protective roles of DEX during acute stress-induced kidney injury are unknown.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

Chen

Feng

et al. 2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Acute stress induces tissue damage through excessive oxidative stress. Dexmedetomidine (DEX) reportedly has an antioxidant effect. However, protective roles and related potential molecular mechanisms of DEX against kidney injury induced by acute stress are unknown. Herein, rats were forced to swim 15 min followed by restraint stress for 3 h with/without DEX (30 μg/kg). Successful model establishment was validated by an open-field test. Assessment of renal function (creatinine, urea nitrogen), histopathology, oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), and apoptosis (transferase-mediated dUTP nick end labeling) was performed. Localization of apoptosis was determined by immunohistochemistry of cleaved caspase 3 protein. In addition, key proteins of the death receptor-mediated pathway, mitochondrial pathway, endoplasmic reticulum stress (ERS) pathway, and ROS/JNK signaling pathway were measured by Western blot. We found that DEX significantly improved renal dysfunction, ameliorated kidney injury, reduced oxidative stress, and alleviated apoptosis. DEX also inhibited the release of norepinephrine (NE), decreased the production of reactive oxygen species (ROS), and inhibited JNK phosphorylation. Additionally, DEX downregulated the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3 proteins in mitochondria-dependent pathways. In summary, DEX protects against acute stress-induced kidney injury in rats by reducing oxidative stress and apoptosis via inhibition of the ROS/JNK pathway.

show abstract

“…Clinical studies have demonstrated that DEX stabilizes perioperative stress-induced hyperglycemia and decreases IR in patients with diabetes; this may be related to a reduction in sympathetic activity, analgesia, and antiinflammatory response [13]. DEX exerted protective effects in lungs by reducing the levels of ERS in a model of ischemia-reperfusion injury [35], and was shown to be closely related to ERS caused by burns and glucose deprivation [12,14,16]. However, the effects of DEX on ERS in an IR model have not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

“…Medium containing 10% CCK-8 reagent was added to the well, followed by incubation for 1-3 h at 37°C. When the color of the medium turned dark orange, optical density at 450 nm (OD 450 ) was measured and a standard curve of cell viability was generated [16].…”

Section: Cell Viability Assaymentioning

confidence: 99%

Dexmedetomidine alleviates insulin resistance in hepatocytes by reducing endoplasmic reticulum stress

Liu

Zhu

et al. 2019

Endocrine

View full text Add to dashboard Cite

Purpose Dexmedetomidine (DEX) stabilizes intraoperative blood glucose levels and reduces insulin resistance (IR), a common perioperative complication. However, the molecular mechanisms underlying these effects remain unclear. Since endoplasmic reticulum stress (ERS) is a mechanism of IR, this study sought to examine whether DEX can effectively alleviate IR by reducing ERS. Methods HepG2 and LO2 cells were treated with different concentrations of insulin. The glucose content assay and Cell Counting Kit-8 (CCK-8) were then employed to determine the optimal insulin concentration capable of inducing IR without affecting cell viability. Insulin-resistant hepatocytes were cultured with different concentrations of DEX for 24 h, and the glucose concentration in the supernatant was measured. ERS was assessed by qPCR and western blotting. The latter was also used to quantify the expression of phosphorylated protein kinase B (p-AKT), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6 phosphatase (G6Pase), which are key proteins involved in the action of insulin. Results After 48-h of culturing with 10 μg/mL insulin, glucose consumption in hepatocytes was found to be reduced. IR hepatocytes cultured with 10, 100, or 1000 ng/ml DEX for 24 h showed a concentration-dependent increase in glucose consumption. Elevated mRNA and protein levels of ERS markers binding immunoglobulin protein (BIP) and ER protein 29 (ERp29), were reversed by DEX treatment. Moreover, reduced p-AKT and increased PEPCK and G6Pase protein levels in IR hepatocytes were also restored following DEX treatment. Conclusion DEX may alleviate IR in hepatocytes by reducing ERS serving to restore insulin action via the IRS-1/PI3K/AKT pathway.

show abstract

Dexmedetomidine protects against oxygen-glucose deprivation/reoxygenation injury-induced apoptosis via the p38 MAPK/ERK signalling pathway

Cited by 26 publications

References 32 publications

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

Dexmedetomidine alleviates insulin resistance in hepatocytes by reducing endoplasmic reticulum stress

Contact Info

Product

Resources

About