Influence of inhalation anesthesia assessed by comprehensive gene expression profiling

Sakamoto, Atsuhiro; Imai, Jun‐ichi; Nishikawa, Akira; Honma, Reiko; Ito, Emi; Yanagisawa, Yuka; Kawamura, Mika; Ogawa, Ryo; Watanabe, Shinya

doi:10.1016/j.gene.2005.03.022

Cited by 77 publications

(71 citation statements)

References 30 publications

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“…To elucidate cellular function, exhaustive analyses of the expression of genes (genomics), proteins (proteomics) and metabolites (metabolomics) have been performed in the brain of rats, which is the main target of general anesthetics. In a previous genomic study, the inhalation anesthetic sevoflurane affected the expression of 1.5% of genes in various rat organs, as detected using a microarray analysis (7). General anesthesia altered the expression levels of genes involved in circadian rhythms; persistent suppression of several circadian genes was identified following treatment of rats with the inhalation anesthetic sevoflurane (8) and the intravenous anesthetics propofol and dexmedetomidine (9).…”

Section: Introductionmentioning

confidence: 91%

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Goto

Hori

Ishikawa

et al. 2014

Molecular Medicine Reports

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Abstract. General anesthesia is commonly used in the surgical arena, but little is known regarding its influence at the genomic and molecular levels. MicroRNAs (miRNAs) belong to a new class of non-coding RNA molecules which influence cell biology. In the present study, it was hypothesized that miRNAs alter gene expression levels under general anesthesia. The aim was to compare the miRNA expression profiles in the rat hippocampus in response to anesthesia with representative volatile (sevoflurane) and intravenous (propofol) anesthetics. Wistar Rats were randomly assigned to either a 2.4% sevoflurane, 600 µg/kg/min propofol or control (without anesthetics) group. Total RNA from hippocampal samples which contained miRNA was subjected to quantitative reverse transcriptionpolymerase chain reaction and Taqman Low-Density Arrays (TLDA). A total of 373 miRNAs are associated with rats and the TLDA analysis revealed that 279 expressed miRNAs (74.8%) were expressed in all three groups. Significant differences in the levels of 33 of the 279 expressed miRNAs (11.8%) were observed among the three groups in response to the anesthetic agents, and when compared with the control group, significant differences were found in 26 of the 279 expressed miRNAs (9.3%). Following sevoflurane anesthesia, the levels of four miRNAs were significantly increased and those of 12 were significantly reduced. By contrast, following propofol anesthesia, the levels of 11 miRNAs were significantly reduced but no miRNAs exhibited significantly elevated levels. Fourteen miRNAs were significantly differentially expressed between the two anesthesia groups. In conclusion, sevoflurane and propofol exerted different effects on miRNA expression in the rat hippocampus.

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Section: Introductionmentioning

confidence: 91%

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Goto

Hori

Ishikawa

et al. 2014

Molecular Medicine Reports

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“…For instance, we found persistent suppression of the expression of several genes implicated in circadian rhythms (e.g., Per2, Dbp, Egr1, Krox20 and NGF1-B) following treatment of rats with sevoflurane (20) and propofol or dexmedetomidine (41). We have also reported changes in the expression of drug metabolising enzymes in rats (e.g., Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2) in response to sevoflurane, isoflurane, propofol, or dexmedetomidine anaesthesia (30,37) The observed changes varied depending on the identity of the anaesthetic used, and also on the mode of administration (inhaled vs. intravenous). Therefore, it is clear that anaesthetics have significant effects on the genomic expression of important regulatory nasia) was obtained from the Animal Experimental Ethical Review Committee of Nippon Medical School (review number: 22-085).…”

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confidence: 60%

“…Eliminating any spots resulting from in-gel trypsin digestion, propofol anaesthesia altered the levels of 39 proteins in the cerebral proteome, with sixteen of these being up-regulated and twenty-three proteins down-regulated. In contrast, sevoflurane anaesthesia altered the levels of 58 procomparison with propofol because it is one of the most commonly used inhaled clinical anaesthetic agents, and we have used it extensively in our previous genomic studies on the effects of anaesthetics on gene expression in the brain (20,37,41). Propofol produces a hypnotic effect by potentiating the gamma-aminobutyric acid-induced chloride current by binding to the beta-subunit of the GABA A receptor (15,32,38).…”

Section: Discussionmentioning

confidence: 99%

Propofol anaesthesia alters the cerebral proteome differently from sevoflurane anaesthesia

Tsuboko

Sakamoto

2011

Biomed. Res.

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Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinaselike-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the timecourse of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.The utility of general anaesthetics is unquestioned, and their harmlessness with regard to mortality and morbidity has been evaluated and endorsed by clinical outcomes (3,(10)(11)(12)24). Little is known, however, regarding their comprehensive influence at the genomic or proteomic level, which is not reflected in mortality and morbidity. A number of genomic studies have been published, and we have shown that general anaesthesia alters gene expression, especially expression of genes involved in circadian rhythms and drug metabolism. For instance, we found persistent suppression of the expression of several genes implicated in circadian rhythms (e.g., Per2, Dbp, Egr1, Krox20 and NGF1-B) following treatment of rats with sevoflurane (20) and propofol or dexmedetomidine (41). We have also reported changes in the expression of drug metabolising enzymes in rats (e.g., Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7, Abcb1a and Abcc2) in response to sevoflurane, isoflurane, propofol, or dexmedetomidine anaesthesia (30, 37) The observed changes varied depending on the identity of the anaesthetic used, and also on the mode of administration (inhaled vs. intravenous). Therefore, it is clear that anaesthetics have significant effects...

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“…In our previous genomic studies, we administered 4.0% or 4.5% sevoflurane for 6 h and showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs (27,31). Here, the reason we experimented with both 2.0% and 4.0% sevoflurane is that inhalation of 4.0% sevoflurane affected circulation (Table 1), and as a result, hypotension, rather than the drug itself, could have affected miRNA expression.…”

Section: Discussionmentioning

confidence: 92%

“…In our previous genomic studies, we showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs (27,31); therefore, we hypothesized that sevoflurane anesthesia also influences miRNA expression in the lung. Using TaqMan low-density arrays (TLDAs), we investigated sevoflurane-dependent changes in miRNA expression in rat lungs.…”

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confidence: 93%

Changes in microRNA expression in rat lungs caused by sevoflurane anesthesia: a TaqMan^|^reg; low-density array study

Tanaka¹,

Ishikawa²,

Arai³

et al. 2012

Biomed. Res.

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Reportedly, a large number of microRNAs (miRNAs) play an important role in inflammatory lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). Sevoflurane is routinely used to various patients, and its safety has been confirmed by clinical outcomes; however, its effects to lungs at the miRNA level have not been elucidated. In our previous genomic studies, we showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs. In this study, we comprehensively investigated changes in miRNA expression caused by sevoflurane anesthesia (2.0% and 4.0%). Sevoflurane anesthesia resulted in apparent changes in miRNA expression in rat lungs, and the pattern of 2.0% sevoflurane-induced changes in miRNA expression was similar to that of 4.0% sevoflurane. Some of the differentially expressed miRNAs are known to be involved in asthma, IPF, and PAH. Especially, miR-146a, the most up-regulated miRNA, is known to attenuate the toxic effects associated with LPS stimulation. We showed, for the first time, dynamic changes in miRNA expression caused by sevoflurane anesthesia, and moreover, our results were important to understand the influence of sevoflurane anesthesia on any patients suffered from various lung diseases.

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Influence of inhalation anesthesia assessed by comprehensive gene expression profiling

Cited by 77 publications

References 30 publications

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia

Propofol anaesthesia alters the cerebral proteome differently from sevoflurane anaesthesia

Changes in microRNA expression in rat lungs caused by sevoflurane anesthesia: a TaqMan^|^reg; low-density array study

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