Isolation and mRNA expression of hypoxia-inducible factor α (HIF-α) in two sublittoral nassariid gastropods: Nassarius siquijorensis and Nassarius conoidalis

2014 ◽  
Vol 99 ◽  
pp. 44-51 ◽  
Author(s):  
C.C. Liu ◽  
P.K.S. Shin ◽  
S.G. Cheung
Keyword(s):  
Mrna Expression ◽  
Hypoxia Inducible Factor ◽  
Factor Α

scholarly journals Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude

2019 ◽  
Vol 116 (48) ◽  
pp. 24006-24011 ◽  
Author(s):  
Tom D. Brutsaert ◽  
Melisa Kiyamu ◽  
Gianpietro Elias Revollendo ◽  
Jenna L. Isherwood ◽  
Frank S. Lee ◽  
...  
Keyword(s):  
Natural Selection ◽  
Aerobic Capacity ◽  
Cellular Response ◽  
Hypoxia Inducible Factor ◽  
Total Sample ◽  
Causal Variant ◽  
Analysis Of Covariance ◽  
Adaptation To Hypoxia ◽  
Spurious Association ◽  
Factor Α

Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO2max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene (EGLN1) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O2 sensor that controls levels of the Hypoxia Inducible Factor-α (HIF-α), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO2max (L⋅min−1 and mL⋅min−1⋅kg−1) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO2max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO2max genotype categories differing by ∼11% (e.g., for rs1769793 SNP genotype TT = 34.2 mL⋅min−1⋅kg−1 vs. CC = 30.5 mL⋅min−1⋅kg−1). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O2 delivery or use during exercise at altitude in Peruvian Quechua.

Anterior Diffuse Retinoblastoma: Mutational Analysis and Immunofluorescence Staining

2009 ◽  
Vol 133 (8) ◽  
pp. 1215-1218
Author(s):  
Michelle B. Crosby ◽  
G. Baker Hubbard ◽  
Brenda L. Gallie ◽  
Hans E. Grossniklaus
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mutational Analysis ◽  
Hypoxia Inducible Factor ◽  
Transforming Growth Factor Β ◽  
Immunofluorescence Staining ◽  
Vascular Endothelial ◽  
Factor Α ◽  
Oxide Synthase ◽  
Endothelial Growth Factor

Abstract Retinoblastoma is the most common primary intraocular tumor of childhood and may be heritable or occur sporadically. Anterior diffuse retinoblastoma is an uncommon variant that is thought to be sporadic. We describe a child with anterior diffuse retinoblastoma who presented with a pseudohypopyon. Genetic analysis showed a germline mutation of the RB1 allele that is potentially heritable. Immunofluorescence staining was positive for transforming growth factor β and for vascular endothelial growth factor and negative for inducible nitric oxide synthase and for hypoxia inducible factor α in the tumor seeds, indicating acquisition of nonischemia-mediated survival factors of the tumor seeds in the aqueous humor.

mTOR inhibition as a possible pharmacological target in the management of systemic inflammatory response and associated neuroinflammation by lipopolysaccharide challenge in rats

2021 ◽  
Author(s):  
Demet Sinem Guden ◽  
Meryem Temiz-Resitoglu ◽  
Sefika Pınar Senol ◽  
Deniz Kibar ◽  
Sakir Necat Yilmaz ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Microglial Activation ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Systemic Inflammatory Response ◽  
Mtor Inhibition ◽  
Factor Α

Neuroinflammation plays a critical role during sepsis triggered by microglial activation. Mammalian target of rapamycin (mTOR) has gained attraction in neuroinflammation, however, the mechanism remains unclear. Our goal was to assess the effects of mTOR inhibition by rapamycin on inflammation, microglial activation, oxidative stress, and apoptosis associated with the changes in the inhibitor-κB (IκB)-α/nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α) pathway activity following a systemic challenge with lipopolysaccharide (LPS). Rats received saline (10 ml/kg), LPS (10 mg/kg), and/or rapamycin (1 mg/kg) via intraperitoneally. Inhibition of mTOR by rapamycin blocked phosphorylated form of ribosomal protein S6, NF-κB p65 activity by increasing degradation of IκB-α in parallel with HIF-1α expression increased by LPS in the kidney, heart, lung, and brain tissues. Rapamycin attenuated the increment in the expression of tumor necrosis factor-α and interleukin-1β, the inducible nitric oxide synthase, gp91<sup>phox</sup>, and p47<sup>phox</sup> in addition to nitrite levels elicited by LPS in tissues or sera. Concomitantly, rapamycin treatment reduced microglial activation, brain expression of caspase-3, and Bcl-2-associated X protein while increased expression of B-cell lymphoma 2 induced by LPS. Overall, this study supports the hypothesis that mTOR contributes to the detrimental effect of LPS-induced systemic inflammatory response associated with neuroinflammation via IκB-α/NF-κB/HIF-1α signaling pathway.

scholarly journals Hypoxia-Inducible Factor α Subunits Regulate Tie2-Expressing Macrophages That Influence Tumor Oxygen and Perfusion in Murine Breast Cancer

2020 ◽  
Vol 205 (8) ◽  
pp. 2301-2311
Author(s):  
Kayla J. Steinberger ◽  
Mary A. Forget ◽  
Andrey A. Bobko ◽  
Nicole E. Mihalik ◽  
Marieta Gencheva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hypoxia Inducible Factor ◽  
Factor Α ◽  
Α Subunits

scholarly journals Expression of MTDH and IL-10 Is an Independent Predictor of Worse Prognosis in ER-Negative or PR-Negative Breast Cancer Patients

2020 ◽  
Vol 9 (10) ◽  
pp. 3153
Author(s):  
Pei-Yi Chu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
En-Pei Isabel Chiang
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Tissue Microarrays ◽  
Breast Cancer Patients ◽  
Worse Prognosis

(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.

scholarly journals Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4796
Author(s):  
Jiali Chen ◽  
Cailin Tang ◽  
Yang Zhou ◽  
Rongfei Zhang ◽  
Shaoxia Ye ◽  
...  
Keyword(s):  
Essential Oil ◽  
Mrna Expression ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Microglial Cells ◽  
Cinnamomum Camphora ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Bv2 Microglial Cells

Cinnamomum camphora (Linn.) Presl has been widely used in traditional Chinese medicine for a variety of purposes. Our previous study indicated the antibacterial mechanism of the essential oil (EO) from C. camphora leaves; however, its anti-inflammatory activity and the underlying mechanism have not been clearly demonstrated. Thus, the present study investigated its anti-inflammatory property. Our data revealed that EO significantly decreased the release of nitric oxide (NO) and the mRNA expression of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced BV2 microglial cells. EO also attenuated LPS-induced increase in the mRNA expression and secretion of inflammatory cytokines including interleukin-6 (IL-6), IL-18, IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the metabolic profiles of LPS-induced BV2 microglial cells treated with or without EO were explored. Thirty-nine metabolites were identified with significantly different contents, including 21 upregulated and 18 downregulated ones. Five pathways were enriched by shared differential metabolites. Compared with the control cells, the glucose level was decreased, while the lactate level was increased, in the culture supernatant from LPS-stimulated cells, which were reversed by EO treatment. Moreover, compared to the LPS-treated group, the activities of phosphofructokinase (PFK) and pyruvate kinase (PK) in EO group were decreased. In summary, the current study demonstrated that EO from C. camphora leaves acts as an anti-inflammatory agent, which might be mediated through attenuating the glycolysis capacity of microglial cells.

scholarly journals HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 134 ◽  
Author(s):  
Mohamed M. Ali ◽  
Shane A. Phillips ◽  
Abeer M. Mahmoud
Keyword(s):  
Dna Methylation ◽  
Interleukin 1 ◽  
Hypoxia Inducible Factor ◽  
Interferon Γ ◽  
The Body ◽  
Human Adipocytes ◽  
Protein Levels ◽  
Factor Α ◽  
Necrosis Factor

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

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