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. 2015 Mar 26;35(6):891–898. doi: 10.1007/s10571-015-0184-8

Anesthetic Propofol Attenuates Apoptosis, Aβ Accumulation, and Inflammation Induced by Sevoflurane Through NF-κB Pathway in Human Neuroglioma Cells

Yue Tian 1, Shanbin Guo 2,✉, Yao Guo 1, Lingyan Jian 2
PMCID: PMC11486239  PMID: 25809614

Abstract

Anesthetics have been reported to promote Alzheimer’s disease neuropathogenesis by inducing amyloid beta (Aβ) protein accumulation and apoptosis. The aim of this study was to evaluate the effect of propofol on the apoptosis, Aβ accumulation, and inflammation induced by sevoflurane in human neuroglioma cells. Human neuroglioma cells were treated with or without sevoflurane and then co-incubated with or without propofol. Cell apoptosis was evaluated by fluorescence-activated cell sorting analysis (FACS) using AV-PI kits, and data showed that apoptosis induced by sevoflurane was significantly attenuated by propofol treatment. In addition, with the reactive oxygen species (ROS) production measured by FACS after staining with dichloro-dihydrofluorescein diacetate, propofol could significantly reduce the production of ROS as well as the accumulation of Aβ induced by sevoflurane assessed by enzyme-linked immuno sorbent assay (ELISA) analysis. On the other hand, the same treatment decreased the inflammation factor production of interleukin-6. Moreover, the level of nuclear factor-kappa B (NF-κB) was tested by Western blot and immunofluorescence assay. We found that the activation of NF-κB pathway was suppressed by propofol. The results suggest that propofol can effectively attenuate the apoptosis, Aβ accumulation, and inflammation induced by sevoflurane in human neuroglioma cells through NF-κB signal pathway.

Keywords: Propofol, Sevoflurane, Human neuroglioma H4 cells, Apoptosis, Aβ accumulation, Inflammation

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disease, which is the most common form of dementia in more than 35 million people worldwide (Querfurth and LaFerla 2010). Earlier studies have shown that there is a growing interest in the potential relationship between general anesthetic exposure and the onset and progression of AD. Evidence from animal models suggests that inhaled anesthetic exposure increases pathology normally associated with AD (Baranov et al. 2009). Also surgery may produce postoperative cognitive dysfunction (Wan et al. 2007). It has been reported that anesthetic sevoflurane (Sev) induced apoptosis in human neuroglioma H4 cells and caused neuronal cell death in the developing rodent brain (Brosnan and Bickler 2013; Xiong et al. 2013). Moreover, Zhang et al. reported that Sev increased the expression of interleukin-6 (IL-6) level through the nuclear factor-kappa B (NF-κB) pathway in H4 cells (Zhang et al. 2013). Hence, it makes sense to identify an anesthetic with neuroprotective effect to suppress the postoperative cognitive dysfunction induced by Sev.

Propofol, one of the widely used anesthetic agents for maintenance of anesthesia for surgical procedures, has been shown to possess pleiotropic characteristics such as anti-inflammatory, anti-oxidant, and neuroprotection activities. (Cui et al. 2014; Li et al. 2014; Zhao et al. 2014). Propofol was demonstrated to reduce inflammatory reaction in ischemic rat brain, which may be associated with the inhibition of inflammatory NF-κB signaling pathway (Shi et al. 2014). Zhang and colleagues reported that propofol attenuates the Sev-induced caspase-3 activation and β-amyloid protein (Aβ) expression (Zhang et al. 2011). The aim of the present study is to evaluate the effect of propofol on Sev-induced apoptosis and inflammatory reaction in H4 cells.

In our study, we investigated the effects of propofol on Sev-induced apoptosis as well as inflammatory reaction in human neuroglioma H4 cells. Moreover, we performed mechanistic studies to determine whether propofol can attenuate the Sev-induced apoptosis, Aβ accumulation, and inflammation in H4 cells. And we found that propofol can effectively attenuate the apoptosis, Aβ accumulation, and inflammation induced by Sev in human neuroglioma cells through NF-κB signal pathway. Our investigation provides a basis for the potential development of propofol in attenuating the postoperative cognitive dysfunction induced by Sev.

Materials and Methods

H4 human neuroglioma cells (naive H4 cells) purchased from China Center for Type Culture Collection were used in this study as an AD research model. Cells were cultured in RPMI-1640 medium (Gibco@, Grand Island, NY, USA) containing 10 % (v/v) heat-inactivated fetal calf serum (HyClone Co., Logan, UT, USA), 100 units/ml penicillin, 100 mg/ml streptomycin, and 2 mM glutamine (all from Gibco@, Grand Island, NY, USA).

Experimental Groups

(1) Control group: treatment with PBS in the same volume as Propofol group; (2) Propofol group: treatment with 100 nM propofol; (3) Sev groups: treatment with 4.1 % Sev; and (4) Propofol + Sev group: treatment with 100 nM propofol plus 4.1 % Sev. Control and Propofol groups were incubated with 21 % O2, 5 % CO2 at 37 °C, while Sev and Propofol + Sev groups were incubated with 21 % O2, 5 % CO2 plus 4.1 % Sev at 37 °C. All groups of cells were treated for 6 h, 21 % O2, 5 % CO2, and 4.1 % Sev were delivered from an anesthesia machine to a sealed plastic box containing the cells in an incubator at 37 °C. The Datex infrared gas analyzer (Puritan–Bennett, Tewksbury, MA, USA) was used to continuously monitor the delivered CO2, O2 and Sev concentrations.

Apoptosis Cells Analysis

Comparative levels of apoptotic cells were determined by flow cytometry to measure the apoptosis rate after staining with propidium iodide (PI) and annexin V. Briefly, cells (1 × 105 cells/ml) treated with or without 100 nM propofol and/or 4.1 % Sev were harvested and washed in cold PBS two times, stained with PI and then detected using Annexin V-FITC apoptosis detection kit (Wan Leibio Co., Shenyang, China) according to the manufacturer’s protocol. Both experiments and apoptosis rates were performed by BD FACS Accuri C6 (Becton–Dickinson, San Jose, USA). Data were analyzed using CELLQuest (Becton–Dickinson, San Jose, USA) software.

Cell Lysis and Protein Amount Quantification

Cells (1 × 105 cells/ml) treated with or without 100 nM propofol and/or 4.1 % Sev were harvested and washed in cold PBS two times. The pellets of the harvested H4 cells were detergent-extracted on ice using an NP-40 lysis buffer (Beyotime Co., Shanghai, China) plus PMSF (Beyotime Co., Shanghai, China) as well as protease inhibitors (Beyotime Co., Shanghai, China) for 30 min on ice. The lysates were collected, centrifuged at 12,000 rpm for 10 min, and quantified for total proteins by a bicinchoninic acid (BCA) protein assay kit (Beyotime Co., Shanghai, China).

Western Blot Analysis

Anti-cleaved caspase-3, anti-Bcl-2, anti-Bax, anti-BACE, anti-IL-6, anti-p-IκBα, anti-IκBα, anti-NF-κB, anti-β-actin, and anti-Histone H3 antibodies were obtained from Cell Signaling Technology (1:1000; Beverly, MA, USA). For Western blot analyses, protein content was determined using BCA Protein Assay Kit (Beyotime Co., Shanghai, China) following manufacturer’s instructions. 40 μg of proteins was separated using 8–12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes (Millipore Co., Billerica, MA, USA). The filters were hybridized with the appropriate primary antibodies overnight at 4 °C. The relative amounts of the transferred proteins were quantified by scanning the autoradiographic films with a gel densitometer and normalized to the corresponding β-actin level except for the level of nuclear NF-κB which was normalized to the Histone H3 level. Quantitative analysis for Western blot was made by Gel-Pro-Analyzer software.

Determination of Intracellular ROS Levels

Intracellular ROS levels were measured using Reactive Oxygen Species Assay Kit (S0033, Beyotime Co., Shanghai, China) by flow cytometry. Briefly, cells (1 × 105 cells/ml) treated with or without 100 nM propofol and/or 4.1 % Sev were harvested and washed in cold PBS two times. After washing with PBS, cells were analyzed using Reactive Oxygen Species Assay Kit (S0033, Beyotime Co., Shanghai, China) according to the manufacturer’s protocol and tested by FACS with excitation and emission wavelengths of 495 and 525 nm, respectively.

ELISA

Cells (1 × 105 cells/ml) treated with or without 100 nM propofol and/or 4.1 % Sev were harvested and washed in cold PBS two times. The concentration of Aβ in H4 cells were determined with the amyloid protein β1-42 (Aβ1-42) assay kit (USCN, Inc., Wuhan, China). According to the manufacturer’s protocol. The concentration levels of Aβ were calculated from a standard curve obtained by the amyloid protein β1-42 (Aβ1-42) assay kit (CEA946Hu, USCN, Inc., Wuhan, China).

Immunofluorescence

Cytoplasmic or nuclear NF-κB protein of H4 cells was identified using a single immunofluorescence staining. Cells treated with or without 100 nM propofol and/or 4.1 % Sev were harvested and fixed in 4 % paraformaldehyde in PBS for 15 min at room temperature (RT) and permeabilized with 0.1 % Tryton X-100 for 30 min. After washes, the slides were treated with 1 % goat serum albumin, (Solarbio, Beijing, China) in PBS solution for 15 min at RT in a wet chamber to reduce non-specific staining and stained with monoclonal antibody NF-κB p65 (1:50, WanLeibio Co., Shenyang, China) at 4 °C overnight. After washing, the slides were labeled with Cy3-labeled Goat Anti-Rabbit IgG (H + L) (1:200, Beyotime Co., Shanghai, China) secondary antibody for 1 h at RT. Both antibodies were diluted in 1 % goat serum albumin in PBS. Samples were stained with DAPI (C1002, biosharp Co., Hefei, China) and observed in an inverted fluorescence microscope (Olympus, Tokyo, Japan); all images were taken at 400× magnification. For negative control, samples were treated without Pro or Sev.

Results

Propofol Attenuates Sev-induced Apoptosis and ROS Production

Propofol has been reported to attenuate caspase-3 activation through the mitochondrial pathway (Shao et al. 2014). To investigate the apoptotic attenuation effect of propofol on Sev-induced H4 cells, the levels of apoptotic cells were determined using apoptosis detection kit with FACS analysis (Fig. 1a). Data showed that propofol alone did not induce apoptosis in H4 cells, while the apoptotic cells were increased in a large degree after treatment with Sev. Interestingly, propofol attenuated the apoptosis induced by Sev after co-incubation with propofol and Sev (Fig. 1a). Apoptotic index was 12.49 ± 1.47 % in Pro plus Sev group, which was lower than Sev group (17.84 ± 1.99 %, P < 0.01, Fig. 1b). Data indicates that propofol attenuated the apoptosis induced by Sev in H4 cells.

Fig. 1.

Fig. 1

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Propofol attenuates Sev-induced apoptosis and ROS production. a, b Apoptosis attenuation induced by propofol in Sev-stimulated H4 cells. Apoptosis induced by Sev or attenuated by propofol was tested by FACS analysis after staining with Annexin V-FITC. Apoptotic cells were fewer in propofol treated cells than that in Sev-stimulated H4 cells (a) and the index of apoptosis was showed in (b). c, d The expression levels of apoptosis-related protein. Levels of cleaved caspase-3, Bcl-2, and Bax after Sev and/or propofol treatment in H4 cells were tested and compared by Western blot analysis (c), and the quantitative analysis of gray intensity was calculated and showed in (d). e, f Propofol inhibited ROS production induced by Sev in H4 cells. ROS content was measured with 2,7′-dihydrofluorescein diacetate (DCFH-DA) after treatment with Sev and/or propofol in H4 cells. Oxidized dihydrofluorescein (DCF) levels were analyzed by FACS. The peak shift to the right indicates increased levels of ROS content meanwhile to the left indicates decreased levels (e). The comparative analysis of ROS levels was calculated and showed in (f). **P < 0.01 versus Sev group; ## P < 0.01 versus control group. Sev sevoflurane, Pro propofol

To determine the mechanisms of apoptosis inhibition by propofol in Sev-induced H4 cells, levels of apoptosis-related proteins were investigated in H4 cells followed by treatment with or without propofol and/or Sev using Western blot analysis. As shown in Fig. 1c, the level of cleaved caspase-3 was detected suggesting that a caspase-mediated pathway led to the apoptosis induced by Sev. Meanwhile, propofol decreased the level of cleaved caspase-3 in H4 cells. Also, activation of the apoptotic pathway is regulated by the balance between pro-apoptotic proteins such as Bax and anti-apoptotic proteins such as Bcl-2 (Willis and Adams 2005). Therefore, the levels of Bax and Bcl-2 were tested in H4 cells induced by Sev with or without propofol. It was found that the level of pro-apoptotic protein Bax was up-regulated, while the level of anti-apoptotic protein Bcl-2 was down-regulated after treatment with Sev. However, propofol down-regulated the high expression of Bax and up-regulated the low level of Bcl-2 induced by Sev (Fig. 2b). Thus, down-regulation of Bax and up-regulation of Bcl-2 seem to account for the inhibition of apoptotic pathway induced by propofol in Sev-stimulated H4 cells.

Fig. 2.

Fig. 2

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Propofol inhibits Aβ accumulation induced by Sev in H4 cells. a, b Propofol down-regulated the level of BACE induced by Sev. The expression level of BACE after Sev and/or propofol treatment in H4 cells was tested and compared by Western blot analysis (a), and the quantitative analysis of gray intensity was calculated and showed in (b). c Propofol inhibits Aβ accumulation induced by Sev in H4 cells. The concentration of Aβ in Sev-induced H4 cells with or without propofol treatment was tested by ELISA analysis. **P < 0.01 versus Sev group; ## P < 0.01 versus control group. Sev sevoflurane, Pro propofol

ROS was then measured by FACS analysis after staining with dichloro-dihydrofluorescein diacetate; Fig. 1e shows that Sev increased the amount of ROS from 7.97 ± 0.83 to 31.28 ± 3.57, P < 0.01; meanwhile, co-inhibition with propofol attenuated Sev-induced ROS accumulation from 31.28 ± 3.57 to 14.08 ± 1.80, P < 0.01, Fig. 1f. These results revealed that ROS plays an important role in Sev-induced apoptosis in H4 cells, which could be inhibited by propofol. Therefore, we suppose that propofol attenuated Sev-induced apoptosis by targeting Bcl-2 via ROS mediated-caspase cascade in H4 cells.

Propofol Inhibits Aβ Accumulation Induced by Sev in H4 Cells

Aβ is reported to be the key component of senile plaques in AD patients (Goate et al. 1991; Masters et al. 1985; Selkoe et al. 1988), which plays a fundamental role in the pathology of AD (Selkoe 2001; Tanzi and Bertram 2005). Also, it is reported that propofol attenuates the isoflurane-induced Aβ oligomerization (Zhang et al. 2011). To investigate the effect of propofol on Sev-induced Aβ accumulation in H4 cells, we tested the level of β-site APP-cleaving enzyme (BACE), which is the catalyzing enzyme of Aβ as well as the concentration of Aβ (Fig. 2). Data showed that the level of BACE was up-regulated by Sev significantly (from 1.00 ± 0.14 to 2.37 ± 0.39), while propofol decreased it to a large degree (from 2.37 ± 0.39 to 1.58 ± 0.20, Fig. 2a, b, P < 0.01). Then we tested the concentration of Aβ and found that the concentration of Aβ was increased by Sev (from 30.49 ± 3.74 to 76.81 ± 10.03, P < 0.01), but after co-treatment with propofol, the concentration of Aβ was almost decreased to the original level (from 76.81 ± 10.03 to 43.0 ± 5.04, P < 0.01, Fig. 2c). These data suggested that the propofol might improve cognitive function by reducing the Aβ levels through down-regulation of the BACE level in H4 cells.

Propofol Inhibits the High Level of IL-6 Expression Induced by Sev and the Activation of NF-κB

It is conceivable that neuroinflammation is associated with the emergence of AD (Akiyama et al. 2000). We therefore determined the effects of the propofol on the levels of the pro-inflammatory cytokine, IL-6, induced by Sev in H4 cells using Western blot analysis. Figure 3a shows that the level of IL-6 was increased by Sev almost twice as much as control. As we expect, propofol decreased the expression level of IL-6 to a large extent (Fig. 3a). The quantitative value of gray intensity analysis of IL-6 in control versus Sev group was 1.00 ± 0.00 versus 2.36 ± 0.24 and in Sev versus Propofol + Sev group was 2.36 ± 0.24 versus 1.22 ± 0.13, respectively (P < 0.01, Fig. 3b).

Fig. 3.

Fig. 3

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Propofol inhibits the high level of IL-6 expression induced by Sev and the activation of NF-κB. a, b Propofol down-regulated the level of pro-inflammatory cytokines IL-6 induced by Sev. The expression level of IL-6 after Sev and/or propofol treatment in H4 cells was tested and compared by Western blot analysis (a), and the quantitative analysis of gray intensity was calculated and showed in (b). c, d Propofol inhibits the activation of NF-κB induced by Sev in H4 cells. The phosphorylation level of IκBα and the distribution levels of NF-κB between cytoplasmic NF-κB p65 and nuclear NF-κB p65 in H4 cells induced by Sev were tested by Western blot analysis (c), and the quantitative analysis of gray intensity was calculated and showed in (d). e The distribution levels between cytoplasmic NF-κB p65 and nuclear NF-κB p65 after Sev and/or propofol treatment in H4 cells were observed by immunofluorescence analysis. **P < 0.01 versus Sev group; ## P < 0.01 versus control group. Sev sevoflurane, Pro propofol

Sev-induced pathological neurodegenerative disorders were reported to be attributed to the increasing level of IL-6 expression (Braida et al. 2004). However, the up-stream mechanism by which Sev increases IL-6 levels remains largely to be determined. Nuclear factor-kappa B (NF-κB) promotes the generation of pro-inflammatory cytokines. To investigate the inactivation of NF-κB caused by propofol in Sev-induced H4 cells, IκBα, the key regulator and inhibitor of NF-κB (Goossens et al. 2011), was tested as well as its phosphorylation level, p-IκBα, in Sev-induced H4 cells. As shown in Fig. 3c, Sev induced the high level of IκBα phosphorylation and the degradation of IκBα, which was reversed by propofol to a great degree (Fig. 3c). The quantitative value of gray intensity analysis showed that pre-treatment with Pro + Sev inhibited the IκBα phosphorylation level from 4.03 ± 0.70 to 1.97 ± 0.29 and the IκBα degradation level from 0.33 ± 0.04 to 0.82 ± 0.10 (P < 0.01, Fig. 3d). Moreover, the levels of NF-κB subunit p65 between both cytoplasmic and nuclear were tested using Western blot analysis (Fig. 3c). Data showed that Sev induced the translocation of cytoplasmic NF-κB p65 subunit into the nucleus. The quantitative value of gray intensity analysis of NF-κB p65 after stimulated with Sev between cytoplasmic and nuclear was 1.00 ± 0.00 versus 0.44 ± 0.05 and 1.00 ± 0.00 versus 3.18 ± 0.39, respectively (P < 0.01, Fig. 3d). As we expected, propofol inhibited Sev-induced translocation of the cytosolic NF-κB p65 subunit into the nucleus, thereby retaining its cytosolic level, and this inhibitory effect was also observed by immunofluorescence analysis (Fig. 3e). As shown in Fig. 3e, the NF-κB p65 immunostaining was evident in the nucleus in Sev-stimulated H4 cells compared with the control group, indicating mainly nuclear localization of NF-κB p65 in Sev-stimulated H4 cells. Propofol treatment significantly attenuated NF-κB p65 translocation and restricted it to the cytoplasm. These results indicate that the inhibitory effect of propofol on the increasing level of IL-6 expression induced by Sev was mediated by NF-κB pathway through the suppression of NF-κB p65 translocation as well as IκBα phosphorylation.

Discussion

Anesthetics have been reported to promote AD neuropathogenesis by inducing Aβ protein accumulation and apoptosis (Wu et al. 2012), which is associated with significant morbidity and mortality and leads to death within three to nine years after diagnosis (Bittner et al. 2011). Recent studies have suggested that the inhalation anesthetics Sev and isoflurane can induce transient insults, including apoptosis, oligomerization of Aβ, and Aβ accumulation, which may potentially contribute to AD neuropathogenesis (Dong et al. 2009; Eckenhoff et al. 2004). Meanwhile, propofol has been well established in general anesthesia and sedation for critical care unit and ambulatory surgery, which has shown to have the ability to scavenge free radical (Hsing et al. 2011) and to protect neuropathogenesis by attenuating caspase activation and apoptosis (Rossaint et al. 2009; Wu et al. 2011). However, the effects of propofol on the Sev-induced apoptosis, as well as the potential underlying mechanisms, have not yet been investigated. Our study first investigated the potential pathway by which propofol attenuated the apoptosis and inflammation of H4 cells induced by Sev. Here we show for the first time that propofol inhibited the apoptosis induced by Sev with the decrease of ROS production stimulated by Sev. Western blot analysis revealed that the activation of apoptosis-related protein such as caspase-3 and Bax induced by Sev was obviously suppressed by propofol in H4 cells induced by ART, in which progress, the expression levels of anti-apoptotic protein Bcl-2 was up-regulated. Moreover, the accumulation of Aβ induced by Sev was inhibited by propofol with the down-regulation of BACE. Also we have found that the inflammatory factor such as IL-6 stimulated by Sev was all decreased by propofol in H4 cells using Western blot analysis. Notably, NF-κB pathway was activated by Sev stimulation while propofol inhibited the translocation of NF-κB from cytoplasm into nucleus through regulation of IκBα phosphorylation. These results revealed that propofol attenuated Sev-induced apoptosis, Aβ accumulation, and inflammation through the NF-κB signaling pathway in H4 cells.

Although some paper reported that propofol induced apoptosis in neurons and oligodendrocytes (Creeley et al. 2013; Pearn et al. 2012; Tagawa et al. 2014), increasing evidence suggests a role for caspase activation and apoptosis in AD neuropathogenesis (Holtzman and Deshmukh 1997; Kim et al. 1997). Dong et al. reported that anesthetic Sev induces apoptosis and increases Aβ protein levels (Dong et al. 2009). In our study, we found that propofol attenuated the cleavage of apoptosis-related protein caspase-3 and Bax induced by Sev in H4 cells. It is known that caspase-3 plays a central role in apoptotic activation (Yin et al. 2011). To the up-stream signaling pathway, the apoptosis is regulated by the interaction between pro-survival proteins such as Bcl-2 and pro-apoptotic proteins such as Bax (Adams and Cory 2007). Bcl-2 binds to Bax and inhibits Bax activation. In our study, we found that the level of Bax expression was down-regulated after propofol treatment. In contrast, the level of Bcl-2 expression was up-regulated. Thus, we consider that propofol targets Bcl-2 to facilitate its inhibition of Bax by preventing the release of pro-apoptotic Bax from a Bax/Bcl-2 heterodimeric complex (Ley et al. 2005), by which propofol exhibited apoptosis attenuation effect (Fig. 1). It was reported that propofol inhibited apoptosis and inflammation through its anti-oxidant activity by scavenging free radicals (Hsing et al. 2011). In our study, levels of ROS production were measured by FACS analysis. We found that Sev induced the production of ROS to a certain degree. Propofol treatment of Sev-induced H4 cells attenuated the production of ROS. According to the present results, we suppose that propofol attenuated Sev-induced apoptosis by targeting Bcl-2 via ROS mediated-caspase cascade in H4 cells. Nonetheless, the precise mechanisms by which propofol attenuated Sev-induced apoptosis need to be further elucidated.

Excessive Aβ accumulation is a major pathological hallmark of AD (Tanzi and Bertram 2005), which is produced via serial proteolysis of the amyloid precursor protein (APP) by aspartyl protease BACE (Xie and Xu 2013). We therefore hypothesized that Sev induced the caspase activation, which then increased the accumulation of BACE; the increased BACE will finally increase Aβ level by facilitating amyloidogenic processing of APP. Our findings showed that Sev induced the up-regulation of BACE expression as well as the enhancement of Aβ level. At the same time, propofol treatment suppressed the accumulation of BACE and the increase of Aβ level induced by Sev, indicating that propofol attenuated Aβ accumulation through the suppression of BACE level (Fig. 2).

NF-κB is a key regulator of inflammatory response, which plays crucial roles in the initiation and progression of AD neuropathogenesis (Akiyama et al. 2000). Song et al. demonstrated that propofol inhibited NF-κB activation resulting in decreased production of the pro-inflammatory cytokines TNF-α and IL-6 (Song et al. 2009). Wu et al. (2009) and Chiu et al. (2009) confirmed the inhibitory effects of propofol on LPS- or lipoteichoic acid-activated NF-κB, respectively. NF-κB is activated by the phosphorylation of IκB primarily of IκBα through the translocation from the cytoplasm to the nucleus (Karin and Ben-Neriah 2000). Here we found that propofol significantly reduced the translocation of NF-κB p65 subunit to nucleus and the phosphorylation of IκBα, which is an endogenous inhibitor of NF-κB in H4 cells induced by Sev. These data indicate that propofol attenuated inflammation through NF-κB signal pathway (Fig. 3).

Conclusion

In the present study, we found that the apoptosis, Aβ accumulation, and inflammation induced by Sev were suppressed by propofol in H4 cells. Moreover, we have studied the potential pathway by which propofol attenuated the apoptosis and inflammation of H4 cells induced by Sev. Propofol attenuated apoptosis through suppression of ROS mediated-caspase cascade in Sev-induced H4 cells, while propofol attenuated Aβ accumulation and inflammation via inhibiting the activation of NF-κB through the down-regulation of p-IκBα in NF-κB signal pathway. These results indicate a novel pharmacological action by propofol for anti-apoptosis, anti-oxidation, and anti-inflammation, which may have implications in discovering the anesthetic with neuroprotective effect in the surgery.

Acknowledgments

This study was supported by a grant from Shengjing Hospital of China Medical University (No. 2014sj08).

Conflict of interest

The authors do not have any possible conflicts of interest.

Footnotes

The original online version of this article was revised: Fig.1 has been updated.

Change history

12/11/2025

The Fig. 1 has been updated.

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