Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner

Daijo, Hiroki; Hoshino, Yuma; Kai, Shinichi; Suzuki, Kazuhiro; Nishi, Kenichiro; Matsuo, Yoshiyuki; Harada, Hiroshi; Hirota, Kiichi

doi:10.1038/srep34424

Cited by 63 publications

(65 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Exposing respiratory cells to WF in vitro , we found a major role for HIF-1α in mediating oxidative-induced PAFR expression. Indeed, increased HIF-1α expression has been found in other exposure settings such as cigarette smoke extract exposure of lung cells and zinc oxide nanoparticle exposure of kidney cells, which indicates that it may be a common exposure response mechanism[29,30]. We also unexpectedly found that HIF-1α mediates PAFR-independent pneumococcal infection in unstimulated respiratory cells.…”

Section: Discussionsupporting

confidence: 54%

Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

Grigg¹,

Miyashita²,

Suri³

2017

PLoS ONE

View full text Add to dashboard Cite

Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR–dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor. We also sought to evaluate the suitability of nasal epithelial PAFR expression in welders as a biomarker of susceptibility to infection. Finally, we investigated the generalisability of the effect of welding fumes on pneumococcal infection and growth using a variety of different welding fume samples. Nasal epithelial PAFR expression in welders and controls was analysed by flow cytometry. WF were collected using standard methodology. The effect of WF on respiratory cell reactive oxygen species production, HIF-1α expression, and pneumococcal infection was determined using flow cytometry, HIF-1α knockdown and overexpression, and pneumococcal infection assays. We found that nasal PAFR expression is significantly increased in welders compared with controls and that WF significantly increased reactive oxygen species production, HIF-1α and PAFR expression, and pneumococcal infection of respiratory cells. In unstimulated cells, HIF-1α knockdown decreased PAFR expression and HIF-1α overexpression increased PAFR expression. However, in knockdown cells pneumococcal infection was paradoxically increased and in overexpressing cells infection was unaffected. Nasal epithelial PAFR expression may be used as a biomarker of susceptibility to pneumococcal infection in order to target individuals, particularly those at high risk such as welders, for the pneumococcal vaccine. Expression of HIF-1α in unexposed respiratory cells inhibits basal pneumococcal infection via PAFR-independent mechanisms.

show abstract

Section: Discussionsupporting

confidence: 54%

Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

Grigg¹,

Miyashita²,

Suri³

2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Indeed, past studies have shown induction of HIF-1α by reactive oxygen species can be reversed by N-acetylcysteine [49]. In contrast, we’ve shown here that the oxidative stress induced by the production of H 2 O 2 , mediated by P-AscH − , results in increased degradation of HIF-1α independent of the function of prolyl hydroxylase.…”

Section: Discussioncontrasting

confidence: 58%

Pharmacologic ascorbate (P-AscH−) suppresses hypoxia-inducible Factor-1α (HIF-1α) in pancreatic adenocarcinoma

Wilkes

O’Leary

et al. 2018

Clin Exp Metastasis

View full text Add to dashboard Cite

HIF-1α is a transcriptional regulator that functions in the adaptation of cells to hypoxic conditions; it strongly impacts the prognosis of patients with cancer. High-dose, intravenous, pharmacological ascorbate (P-AscH−), induces cytotoxicity and oxidative stress selectively in cancer cells by acting as a pro-drug for the delivery of hydrogen peroxide (H2O2); early clinical data suggest improved survival and inhibition of metastasis in patients being actively treated with P-AscH−. Previous studies have demonstrated that activation of HIF-1α is necessary for P-AscH− sensitivity. We hypothesized that pancreatic cancer (PDAC) progression and metastasis could be be targeted by P-AscH− via H2O2-mediated inhibition of HIF-1α stabilization. Our study demonstrates an oxygen- and prolyl hydroxylase-independent regulation of HIF-1α by P-AscH−. Additionally, P-AscH− decreased VEGF secretion in a dose-dependent manner that was reversible with catalase, consistent with an H2O2-mediated mechanism. Pharmacological and genetic manipulations of HIF-1α did not alter P-AscH−-induced cytotoxicity. In vivo, P-AscH− inhibited tumor growth and VEGF expression. We conclude that P-AscH− suppresses the levels of HIF-1α protein in hypoxic conditions through a post-translational mechanism. These findings suggest potential new therapies specifically designed to inhibit the mechanisms that drive metastases as a part of PDAC treatment.

show abstract

“…Antibodies againt HIF-2 α /EPAS1 were obtained from Novus Biologicals (Littleton, CO). Isoflurane and mouse monoclonal antibodies to α -tubulin were obtained from FUJIFILM Wako Pure Chemical (Osaka, Japan) [15][16][17] (Table 1).…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

Cancerous phenotypes associated with hypoxia-inducible factors are not influenced by the volatile anesthetic isoflurane in renal cell carcinoma

Sumi

Matsuo

Kusunoki

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Cancerous phenotypes associated with hypoxia-inducible factors are not influenced by the volatile anesthetic isoflurane in renal cell carcinoma Hypoxia-inducible factors are not activated by isoflurane Abstract The possibility that anesthesia during cancer surgery may affect cancer recurrence, metastasis, and patient prognosis has become one of the most important topics of interest in cancer treatment. For example, the volatile anesthetic isoflurane was reported in several studies to induce hypoxia-inducible factors, and thereby enhance malignant phenotypes in vitro. Indeed, these transcription factors are considered critical regulators of cancer-related hallmarks, including "sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis, invasion, and metastasis." This study aimed to investigate the impact of isoflurane on the growth and migration of derivatives of the renal cell line RCC4. We indicated that isoflurane treatment did not positively influence cancer cell phenotypes, and that hypoxia-inducible factors (HIFs) maintain hallmark cancer cell phenotypes including gene expressions signature, metabolism, cell proliferation and cell motility. The present results indicate that HIF activity is not influenced by the volatile anesthetic isoflurane.7.5% sodium dodecyl sulfate-polyacrylamide, gel electrophoresis and electro-transferred to membranes, probed with 1:2,000 of the indicated primary antibodies, probed with 1:8,000 of donkey anti-rabbit IgG (GE Healthcare, Piscataway, NJ) or sheep anti-mouse IgG (GE Healthcare) conjugated with horseradish peroxidase, and visualized with enhanced Chemi-Lumi One Super (Nacalai Tesque, Kyoto, Japan) (S1 Figure). Bands were quantified via densitometric analysis using Image Studio Lite (LI-COR Biosciences, Lincoln, NE, USA) [15,20,21]. Experiments were performed in triplicate, and representative blots are shown. Detailed protocols are available at protocols.io (dx.doi.org/10.17504/protocols.io.x9mfr46). Semi-quantitative real-time reverse transcriptase-polymerase chain reaction analysis (qRT-PCR) analysisTotal RNA was extracted from cells using RNeasy™ Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. First-strand synthesis and RT-PCR were performed using QuantiTect™ Reverse Transcription Kit (Qiagen) andRotor-Gene™ SYBR Green PCR Kit (Qiagen), following the manufacturer's protocol.Targets were amplified and quantified in Rotor-Gene Q™ (Qiagen) and the expression fold-change of each target mRNA was normalized to that of β -actin. SLC2A1 was quantified with the QuantiTect Primer Assay QT00068957, while VEGFA was quantified with forward primer 5'-AGCCTTGCCTTGCTGCTCT-3' and reverse primer 5'-TCCTTCTGCCATGGGTGC-3'. HIF1A was quantified using the forward and reverse primers 5'-ACACACAGAAATGGCCTTGTGA-3' and 5'-CCTGTGCAGTGCAATACCTTC-3', while EPAS1(HIF2A) was quantified with the forward and reverse primers 5'-ATGGGACTTACACAGGTGGAG-3' and 5'-GCTCTGTGGACATGTCTTTGC-3'.

show abstract

Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner

Cited by 63 publications

References 56 publications

Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha

Pharmacologic ascorbate (P-AscH−) suppresses hypoxia-inducible Factor-1α (HIF-1α) in pancreatic adenocarcinoma

Cancerous phenotypes associated with hypoxia-inducible factors are not influenced by the volatile anesthetic isoflurane in renal cell carcinoma

Contact Info

Product

Resources

About