Dexmedetomidine inhibits activation of the MAPK pathway and protects PC12 and NG108-15 cells from lidocaine-induced cytotoxicity at its maximum safe dose

Wang, Qiong; Tan, Yonghong; Zhang, Na; Xu, Yingyi; Wei, Wei; She, Ying-Jun; Bi, Xiaobao; Zhao, Baisong; Ruan, Xiuxiu

doi:10.1016/j.biopha.2017.04.084

Cited by 16 publications

(16 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that dexmedetomidine exerts kidney protection [43] and lung protective effects [44] via inhibition of the MAPK signaling pathway but attenuates neuroapoptosis via activation of this pathway [45,46]. In the present study, we found miRNA-101-3p to be significantly downregulated.…”

Section: Discussionsupporting

confidence: 65%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Circulating miRNAs could serve as biomarkers for diagnosis or prognosis of heart diseases and cerebrovascular diseases. Dexmedetomidine has protective effects in various organs. The effects of dexmedetomidine on circulating miRNAs remain unknown. Here, we investigated differentially expressed miRNA and to predict the target genes of the miRNA in patients receiving dexmedetomidine. Methods: The expression levels of circulating miRNAs of 3 patients were determined through high through-put miRNA sequencing technology. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 7.1 and miRDB v.5. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional annotation and pathway enrichment analysis of target genes respectively. Results: Twelve differentially expressed miRNAs were identified. Five miRNAs were upregulated (hsa-miR-4508, hsa-miR-novel-chr8_87373, hsa-miR-30a-3p, hsa-miR-novel-chr16_26099, hsa-miR-4306) and seven miRNAs (hsa-miR-744-5p, hsa-miR-320a, hsa-miR-novel-chr9_90035, hsa-miR-101-3p, hsa-miR-150-5p, hsa-miR-342-3p, and hsa-miR-140-3p) were downregulated after administration of dexmedetomidine in the subjects. The target genes and pathways related to the differentially expressed miRNAs were predicted and analyzed. Conclusion: The differentially expressed miRNAs may be involved in the mechanisms of action of dexmedetomidine. Specific miRNAs, such as hsa-miR-101-3p, hsa-miR-150-5p and hsa-miR-140-3p, are new potential targets for further functional studies of dexmedetomidine.

show abstract

Section: Discussionsupporting

confidence: 65%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…However, these strategies are not always successful 8. In our previous studies, we reported that dexmedetomidine can be used to alleviate LA-induced neurological damage in PC12 andNG108-15 cells 19,20. In the present study, we further show a possible mechanism by which administration of DEX alleviates neurological damage provoked by lidocaine in PC12 cells (Figure 7).…”

Section: Discussionsupporting

confidence: 59%

“…According to our previous study,20 which indicates 100–150 μM is the maximum safe dose of DEX for PC12 cells (Figure 1A). Moreover, 40–150 µM DEX has no significant differentiation in protecting cells from lidocaine-induced injury.…”

Section: Resultsmentioning

confidence: 65%

“…In fact, a recent study showed that DEX alleviated lidocaine-induced spinal neurotoxicity via regulating PKC expression in a rat model 18. Similarly, our previous studies demonstrated that DEX protected PC12 cells from lidocaine-induced cytotoxicity via inhibiting COL3A1 expression and MAPK pathway activation 19,20. However, the rational for DEX combined with lidocaine to reduce lidocaine-induced neurotoxicity in the clinical setting remains to be further studied, especially in the mechanism considering a diversity of biological activities of DEX.…”

Section: Introductionmentioning

confidence: 88%

See 1 more Smart Citation

<p>Dexmedetomidine protects PC12 cells from lidocaine-induced cytotoxicity via downregulation of Stathmin 1</p>

Tan¹,

Bi²,

Wang³

et al. 2019

DDDT

Self Cite

View full text Add to dashboard Cite

Background: Understanding of lidocaine-induced neurotoxicity is not complete, resulting in the unsuccessful treatment in some clinical settings. Dexmedetomidine (DEX) has been shown to alleviate lidocaine-induced neurotoxicity in our previous cell model. However, the rationale for DEX combined with lidocaine to reduce lidocaine-induced neurotoxicity in the clinical setting remains to be further clarified in the detailed molecular mechanism. Methods: In this study, we established a cellular injury model by lidocaine preconditioning. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2ʹ-deoxyuridine (EdU) proliferation assay kit were used to analyze cell proliferation. Cell apoptosis was measured by flow cytometry and Hoechst 33342 staining. Cell cycle progression was detected by flow cytometry. The protein expression levels were detected by Western blotting and immunofluorescence staining. Results: Our results showed that DEX dose-dependently restored impaired proliferation of PC12 cells induced by lidocaine，as reflected by the increased cell viability and EdU positive cells, which were consistent with the decreased expression of tumor suppressor protein p21 and increased expression of cell cycle-related cyclin D1 and CDK1. In addition, DEX dose-dependently reduced apoptotic PC12 cells induced by lidocaine，as reflected by the decreased expression of apoptosis-related Bax, caspase-3 and caspase-9 and increased expression of anti-apoptotic Bcl-2 compared to the cells only treated with lidocaine. Mechanistically, with gain-or-loss-of-function of STMN1, we showed that DEX-mediated neuroprotection by lidocaine-induced damage is associated with downregulation of STMN1 which might be an upstream molecule involved in regulation of mitochondria death pathway. Conclusion: Our results reveal that DEX is likely to be an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.

show abstract

“…Chen et al ( 18 ) have demonstrated that Dex exerts protective effects on postoperative cognitive dysfunction by downregulating the expression levels of inflammatory factors interleukin (IL)-1β, tumor necrosis factor (TNF)-α and NF-κB in rats. Wang et al ( 19 ) have investigated the mechanism of lidocaine-induced cytotoxicity and reported that the anti-inflammatory effect of Dex may be achieved by suppressing the mitogen-activated protein kinase (MAPK) signaling pathway to affect the expression of caspase-3 and Bcl-2 and reduce apoptosis. Additionally, Dex has been reported to reduce the expression of macrophage inflammatory protein-2 and other cytokines (TNF-α, IL-6 and IL-1β) in rat lung cells ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of dexmedetomidine on hypoxia/reoxygenation injury in cardiomyocytes by regulating the CHOP signaling pathway

Shi

Liu

2020

Mol Med Rep

View full text Add to dashboard Cite

Hypoxia/reoxygenation (H/r) injury in myocardial cells occurs frequently during cardiac surgery and affects the prognosis of patients. The present study aimed to investigate the protective effects of dexmedetomidine (dex) on H/r injury and its association with the c/eBP-homologous protein (cHoP) signaling pathway. an H/r model was constructed in H9c2 cells to investigate the effects of dex on H/r injury. cell viability, apoptosis and lactate dehydrogenase (LDH) levels were determined by MTT, flow cytometry and 2,4-dinitrophenylhydrazine colorimetric assays, respectively. The expression levels of inflammatory factors were measured by reverse transcription-quantitative Pcr (rT-qPcr), and cHoP and glucose-regulated protein-78 (Grp78) expression levels were detected by rT-qPcr and western blotting. cHoP was overexpressed or knocked down to detect the cell viability, apoptosis, LDH level and the expression levels of inflammatory factors and Grp78. The results demonstrated that in the H/r group, cell viability was lower and apoptosis was higher, and that higher levels of LDH and inflammatory factors were present compared with those in the dex+H/r group. Silencing of CHOP significantly reversed the H/R-reduced cell viability, high apoptotic rate and ldH levels, as well as the elevated expression levels of inflammatory factors and Grp78 caused by H/r injury, whereas the overexpression of cHoP inhibited cell viability and promoted apoptosis, elevated ldH level and expression of inflammatory factors and Grp78 compared with the negative control. additionally, pretreatment with Dex significantly alleviated the H/R injury; thus, Dex may protect H9c2 cells against H/r induced cell injury, possibly by suppressing the cHoP signaling pathway.

show abstract

Dexmedetomidine inhibits activation of the MAPK pathway and protects PC12 and NG108-15 cells from lidocaine-induced cytotoxicity at its maximum safe dose

Cited by 16 publications

References 24 publications

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

<p>Dexmedetomidine protects PC12 cells from lidocaine-induced cytotoxicity via downregulation of Stathmin 1</p>

Protective effects of dexmedetomidine on hypoxia/reoxygenation injury in cardiomyocytes by regulating the CHOP signaling pathway

Contact Info

Product

Resources

About