Up-regulation of Hypoxia Inducible Factor 1α by Isoflurane in Hep3B Cells

Li, Qi Fang; Wang, Xiang Rui; Yang, Yue Wu; Su, Dian San

doi:10.1097/00000542-200612000-00021

Cited by 60 publications

(55 citation statements)

References 51 publications

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“…Studies carried out by a number of laboratories have found that the predominant mechanism in this induction is an increase in HIF-1␣ protein translation via the PI3K pathway and mitogen-activated protein kinase pathway (32). Meanwhile, we recently have reported that volatile anesthetic isoflurane stimulates HIF-1␣ protein synthesis in the human hepatoma cell line Hep3B cells (29). So we focused first on the two pathways as a potential part of the intracellular signaling cascade activated by TNF␣/IL-4 in BEAS-2B cells.…”

Section: Discussionmentioning

confidence: 97%

“…The small interference RNA (siRNA) oligonucleotide for HIF-1␣ was designed as we described previously (29). Sense and antisense RNA strands for HIF-1␣-siRNA: 5=-UGU GAG UUC GCA UCU UGA UTT-3= and 5=-AUC AAG AUG CGA ACU CAC ATT-3=; for p65-siRNA: 5=-CUC AAG AUC UGC CGA GUA ATT -3= and 5=-UUA CUC GGC AGA UCU UGA GTT-3= were commercially synthesized (Genetimes Technology, Shanghai, China).…”

Section: Cells and Reagentsmentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory stimulation and hypoxia cooperatively activate HIF-1α in bronchial epithelial cells: involvement of PI3K and NF-κB

Jiang

Zhu

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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The transcription factor hypoxia-inducible factor (HIF)-1 plays a central physiological role in oxygen and energy homeostasis, and is activated during hypoxia by stabilization of the subunit HIF-1α. Recent studies have demonstrated that non-hypoxic stimuli can also activate HIF-1α in a cell-specific manner. Here, we demonstrate that stimulation of BEAS-2B cells and primary human bronchial epithelial cells by proinflammatory cytokines TNFα/IL-4 strongly induced expression and transcriptional activity of HIF-1α under normoxic conditions and amplified hypoxic HIF-1α activation. TNFα/IL-4 stimulated de novo HIF-1α gene transcription and translation rather than affected HIF-1α protein degradation and mRNA decay process. The activation of HIF-1α by TNFα/IL-4 was countered by the phosphoinositol 3-kinase (PI3K) inhibitor LY-294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the MAPK pathway. In line, TNFα/IL-4 also activated NF-κB, whereas blocking of NF-κB by an inhibitor or silencing NF-κB subunit p65 attenuated HIF-1α activation by TNFα/IL-4. We also found the collaborative induction of VEGF, a potent angiogenic factor required for airway remodeling, by TNFα/IL-4 and hypoxia partially via HIF-1α pathway in BEAS-2B cells. This study reports the previously unsuspected collaborative regulation of HIF-1α by TNFα/IL-4 and hypoxia in bronchial epithelial cells partially via PI3K-mTOR and NF-κB pathway, and thereby will lead to the elucidation of the importance of HIF-1 in integrating inflammatory and hypoxic response in the pathogenesis of airway diseases.

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Section: Discussionmentioning

confidence: 97%

Section: Cells and Reagentsmentioning

confidence: 99%

Inflammatory stimulation and hypoxia cooperatively activate HIF-1α in bronchial epithelial cells: involvement of PI3K and NF-κB

Jiang

Zhu

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The beneficial effect of isoflurane preconditioning may originate from its ability to induce endogenous cytoprotective pathways, such as the HO-1 pathway. Our group has previously reported that isoflurane induces HO-1 accumulation and that this effect is associated with the activation of the transcription factor HIF-1 in vitro [9,10] . Other groups have demonstrated the induction of HO-1 by isoflurane in liver tissue in vivo [11,12] .…”

Section: Introductionmentioning

confidence: 91%

“…Isoflurane pretreatment of the cells was performed in an airtight chamber, as previously described [9] . Briefly, cell dishes were kept in an airtight chamber that was housed within a water-jacketed incubator maintained at 37 °C.…”

Section: Isoflurane Exposure and Application Of Chemicalsmentioning

confidence: 99%

Heme oxygenase-1 mediates the anti-inflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages

Zhu

Jiang

et al. 2009

Acta Pharmacol Sin

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Aim:The aim of this study was to investigate the anti-inflammatory action of isoflurane preconditioning in a model of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages and examine the role of heme oxygenase (HO)-1 in this process. Methods: Murine 264.7 macrophages were pretreated with or without 1%-3% isoflurane for 1 h. Thirty minutes later, the cells were incubated with or without LPS for 24 h. Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell injury was assessed by measuring the release of lactate dehydrogenase (LDH). HO-1 and inducible nitric oxide synthase (iNOS) protein expression was analyzed by Western blotting. Tumor necrosis factor (TNF)-α levels, nitrite production and HO activity were also determined. Results: Pretreatment with the nontoxic and clinically approved anesthetic isoflurane potently attenuated the cell injury and the decrease in cell viability that was induced by LPS. Treatment or pretreatment with 2% isoflurane induced HO-1 protein expression and caused an induction of HO activity. This result correlated with a decrease in iNOS expression, a decrease in the production of nitric oxide (NO) and impaired release of TNF-α in LPS-stimulated macrophages. Blockade of HO activity with tin protoporphyrin (SnPP) reversed these effects. Conclusion: Isoflurane preconditioning exerts its anti-inflammatory activity through the HO-1 pathway in an in vitro inflammation model.

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“…In hypoxic cells with accumulation of HIF-1 both halothane and propofol inhibit the HIF-1 accumulation [17,18]. It is reported that isoflurane and xenon enhance HIF-1 accumulation during hypoxia [19][20][21].…”

Section: Hif-1 Related Oxygen Sensingmentioning

confidence: 99%

Oxygen Aspects on Sensing and Utilization

Moriyama¹

2015

Glob J Anesth

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Oxygen is known to be one of the strongest electron acceptors and has one of its main functions in the electron transport chain producing ATP and heat, so important for energy expenditure and thermoregulation. However, some important mechanisms of oxygen functions are not completely delineated, yet. Sensing oxygen is purposeful and serves various specific functions. One mode of action is to initiate afferent neuronal activity which requires increased cytosolic Ca 2+ concentrations. Another action is linked to the Hypoxia Inducible Factor, HIF-1, which in the normoxic state is produced in a prolyl-hydroxylase regulated reaction. The calcium generated neuronal response is usually described as a quick, acute, response that is set in action within seconds whereas the HIF related responses are slower, chronic, activated after several minutes to hours. Traditionally, it has been the opinion that oxygen can diffuse freely across plasma membranes. However, the lipid bilayer has higher viscosity than water by several times, and high oxygen permeability has not been proven. Hence, oxygen transportation across plasma or cell membranes cannot be explained by diffusion alone. It is therefore justified to ask the question if a specific oxygen channel or transport mechanism remains to be discovered.

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Up-regulation of Hypoxia Inducible Factor 1α by Isoflurane in Hep3B Cells

Abstract: Isoflurane can up-regulate HIF-1alpha and enhance HIF-1-responsive genes heme oxygenase 1, inducible nitric oxide synthase, and VEGF mRNA expression in Hep3B cells. The induction of HIF-1alpha by isoflurane does not involve protein degradation but depends on translation pathway.

Cited by 60 publications

References 51 publications

Inflammatory stimulation and hypoxia cooperatively activate HIF-1α in bronchial epithelial cells: involvement of PI3K and NF-κB

Inflammatory stimulation and hypoxia cooperatively activate HIF-1α in bronchial epithelial cells: involvement of PI3K and NF-κB

Heme oxygenase-1 mediates the anti-inflammatory effect of isoflurane preconditioning in LPS-stimulated macrophages

Oxygen Aspects on Sensing and Utilization

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