Mutation of isocitrate dehydrogenase 1 induces glioma cell proliferation via nuclear factor-κB activation in a hypoxia-inducible factor 1-α dependent manner

Hypoxia-inducible factor-1 (HIF-1) is a regulator of metabolic adaptation to hypoxia. It is now appreciated that HIF-1α accumulation is achieved under normoxic conditions by various factors, such as TNF-α. Here, it was our intention to gain insight into the signaling mechanisms used by TNF-α to stimulate HIF-1α. In tubular LLC-PK1or human embryonic kidney cells, TNF-α induced accumulation of HIF-1α protein but not HIF-1α mRNA. Blocking nuclear factor (NF)-κB with sulfasalazine or expression of an IκB superrepressor attenuated HIF-1α accumulation, whereas transfection of active p50/p65-NF-κB subunits mimicked a TNF-α response. Experiments with actinomycin D and cycloheximide also pointed to a transcriptional and translational process in facilitating the TNF-α response. Interestingly, and in contrast to established hypoxic signaling concepts, TNF-α elicited HIF-1α accumulation in a ubiquitinated form that still bound the von Hippel-Lindau (pVHL) protein. These data indicate that HIF-1α accumulation by TNF-α demands the NF-κB pathway, preserves ubiquitination of HIF-1α, and allows the HIF-1α-pVHL interaction.

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Correction to: MiR-126 Regulates the ERK Pathway via Targeting KRAS to Inhibit the Glioma Cell Proliferation and Invasion

Molecular Neurobiology ◽

10.1007/s12035-021-02302-3 ◽

2021 ◽

Author(s):

Yang Li ◽

Yunqian Li ◽

Pengfei Ge ◽

Chengyuan Ma

Keyword(s):

Cell Proliferation ◽

Glioma Cell ◽

Erk Pathway ◽

Glioma Cell Proliferation ◽

Proliferation And Invasion

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Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

Infection and Immunity ◽

10.1128/iai.68.12.7087-7093.2000 ◽

2000 ◽

Vol 68 (12) ◽

pp. 7087-7093 ◽

Cited By ~ 28

Author(s):

Y.-H. Li ◽

Z.-Q. Yan ◽

J. Skov Jensen ◽

K. Tullus ◽

A. Brauner

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Alveolar Macrophages ◽

Nuclear Factor Κb ◽

Inos Expression ◽

Dependent Manner ◽

Nuclear Factor ◽

Oxide Synthase ◽

Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

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