ArticlePloS one2012
Regulation of NF-κB activation through a novel PI-3K-independent and PKA/Akt-dependent pathway in human umbilical vein endothelial cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Jiangfu Fuwei granules alleviate chronic atrophic gastritis by suppressing angiogenesis through the PI3K-AKT-HIF1α pathway.American journal of translational research · 2026Article
- Signaling pathways and ion channels in osteoarthritis: a review of recent advances.Frontiers in immunology · 2026Review
- Pulchinenoside C Attenuates the Development of Osteoarthritis by Inhibiting the PI3K/AKT/NF-κB Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Traditional Chinese medicine in the treatment ofWorld journal of gastroenterology · 2025Review
- Investigating the effects ofHeliyon · 2024Article
- Article
- β-endorphin suppresses ultraviolet B irradiation-induced epidermal barrier damage by regulating inflammation-dependent mTORC1 signaling.Scientific reports · 2023Article
- Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways.iScience · 2023Article
- Morin Inhibits Dox-Induced Vascular Inflammation By Regulating PTEN/AKT/NF-κB Pathway.Inflammation · 2022Article
- AMIGO2 contained in cancer cell-derived extracellular vesicles enhances the adhesion of liver endothelial cells to cancer cells.Scientific reports · 2022Article
- Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Saponins from Tribulus terrestris L. Extract Down-regulate the Expression of ICAM-1, VCAM-1 and E-selectin in Human Endothelial Cell Lines.International journal of molecular and cellular medicine · 2020Article
- The Antioxidant MitoQ Protects Against CSE-Induced Endothelial Barrier Injury and Inflammation by Inhibiting ROS and Autophagy in Human Umbilical Vein Endothelial Cells.International journal of biological sciences · 2019Article
- Contribution of myo-inositol oxygenase in AGE:RAGE-mediated renal tubulointerstitial injury in the context of diabetic nephropathy.American journal of physiology. Renal physiology · 2018Article
- Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses.Scientific reports · 2016Article
- Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice.Scientific reports · 2016Article
- Article
- Involvement of the Akt/NF-κB pathways in the HTNV-mediated increase of IL-6, CCL5, ICAM-1, and VCAM-1 in HUVECs.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor NF-κB regulates numerous inflammatory diseases, and proteins involved in the NF-κB-activating signaling pathway are important therapeutic targets. In human umbilical vein endothelial cells (HUVECs), TNF-α-induced IκBα degradation and p65/RelA phosphorylation regulate NF-κB activation. These are mediated by IKKs (IκB kinases) viz. IKKα, β and γ which receive activating signals from upstream kinases such as Akt. Akt is known to be positively regulated by PI-3K (phosphoinositide-3-kinase) and differentially regulated via Protein kinase A (PKA) in various cell types. However, the involvement of PKA/Akt cross talk in regulating NF-κB in HUVECs has not been explored yet. Here, we examined the involvement of PKA/Akt cross-talk in HUVECs using a novel compound, 2-methyl-pyran-4-one-3-O-β-D-2',3',4',6'-tetra-O-acetyl glucopyranoside (MPTAG). We observed that MPTAG does not directly inhibit IKK-β but prevents TNF-α-induced activation of IKK-β by blocking its association with Akt and thereby inhibits NF-κB activation. Interestingly, our results also revealed that inhibitory effect of MPTAG on Akt and NF-κB activation was unaffected by wortmannin, and was completely abolished by H-89 treatment in these cells. Thus, MPTAG-mediated inhibition of TNF-α-induced Akt activation was independent of PI-3K and dependent on PKA. Most importantly, MPTAG restores the otherwise repressed activity of PKA and inhibits the TNF-α-induced Akt phosphorylation at both Thr308 and Ser473 residues. Thus, we demonstrate for the first time the involvement of PKA/Akt cross talk in NF-κB activation in HUVECs. Also, MPTAG could be useful as a lead molecule for developing potent therapeutic molecules for diseases where NF-κB activation plays a key role.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.