Bleomycin-induced nuclear factor-κB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3β

Ma, Yan; Wang, Manxiang; Li, Naping; Wu, Renliang; Wang, Xi

doi:10.1016/j.toxlet.2009.02.023

Cited by 17 publications

(19 citation statements)

References 30 publications

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“…GSK-3beta can phosphorylate NF-kappaB at S468 which promoted its proteasomal degradation [80]. GSK-3beta also interacted with I-kappaBalpha in epithelial cells [81]. Other studies have indicated that GSK-3beta suppressed NF-kappaB activity by preventing the degradation of IkapaBalpha [82].…”

Section: Biochemical Functions Of Gsk-3mentioning

confidence: 99%

GSK-3 as potential target for therapeutic intervention in cancer

et al. 2014

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The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.

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Section: Biochemical Functions Of Gsk-3mentioning

confidence: 99%

GSK-3 as potential target for therapeutic intervention in cancer

et al. 2014

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“…GSK3b has been shown to phosphorylate p65 at Ser468 and negatively regulate its activity by promoting its degradation (Buss et al 2004). Recent reports suggest that active GSK3b physically interacts with IjBa in normal epithelial cells (Ma et al 2009) and then blocks NF-jB-dependent transcription by preventing IjBa degradation (Sanchez et al 2003). In contrast, our recent studies have demonstrated that inactivation of GSK3 suppressed the transcription of NF-jBmediated inflammatory cytokine production by decreasing the amount of cAMP response element-binding protein (CREB)-binding protein available to NF-jB (Wang et al 2011b).…”

Section: Gsk3b Affects Tumorigenesis Of Ec Through Transcription Factmentioning

confidence: 87%

The Role of Glycogen Synthase Kinase 3-β in Immunity and Cell Cycle: Implications in Esophageal Cancer

Gao

Brown

Wang

et al. 2013

Arch. Immunol. Ther. Exp.

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Esophageal cancer (EC) is one of the most aggressive gastrointestinal malignancies, possessing an insidious onset and a poor prognosis. Numerous transcription factors and inflammatory mediators have been reported to play a pivotal role in the initiation and progression of this cancer. However, the specifics of the signaling network responsible for said factors, especially which elements are the critical regulators, are still being elucidated. Glycogen synthesis kinases 3 (GSK3)b was originally regarded as a kinase regulating glucose metabolism. Accumulating evidence demonstrated that it also played an essential role in a variety of cellular processes including proliferation, differentiation, inflammation, motility, and survival by regulating various transcription factors such as c-Jun, AP-1, b-catenin, CREB, and NF-jB. Aberrant regulation of GSK3b has been shown to promote cell growth in some cancers, while suppressing it in others, and thus may play an important role in the development of EC. This review will discuss our current understanding of GSK3b signaling, and its control of the expression and activation of various transcription factors that mediate the inflammatory response. We will also explore some of the known mediators of EC progression, and based on current literature, elucidate the potential roles and implications of GSK3 in this disease.

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“…Inducible NF-B activation depends on the phosphorylationinduced proteosomal degradation of the inhibitor of NF-B proteins (IBs, such as IB␣), which retain inactive NF-B dimers in the cytosol in unstimulated cells (11,12). Previous studies have reported that the intratracheal administration of BLM induced the phosphorylation and degradation of IB␣ and the translocation of the active dimer of NF-B into the nucleus in the whole lungs of mice (10,27). In the present study, we demonstrated the inhibitory effect of RKT administration on NF-B signaling through both the suppression of the expression levels of phosphorylated NF-B p65 and NF-B p65 protein in the cytoplasm and the retention of the cytosolic IB␣ protein levels in BLM-treated lungs.…”

Section: Discussionmentioning

confidence: 99%

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner

Tsubouchi

Yanagi

Miura

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Acute lung injury (ALI) is a critical syndrome consisting of acute respiratory failure associated with extensive pulmonary infiltrates. The pathological characterization of ALI includes injuries of alveolar epithelial cells (AECs), alveolar neutrophilic infiltration, and increases in proinflammatory cytokines, which cause destruction of the alveolar capillary barrier and subsequent devastating lung fibrosis. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment of patients with gastrointestinal symptoms and is known to stimulate ghrelin secretion. The therapeutic effects of RKT on organ inflammation and fibrosis remain unknown. We investigated the pharmacological potential of RKT in the treatment of ALI by using a bleomycin-induced ALI model in mice. RKT or distilled water (DW) was given to mice daily starting 12 h after bleomycin administration. The RKT-treated mice showed a definitively higher survival rate than the DW-treated mice after injury. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of proinflammatory cytokines, activation of the NF-κB pathway, apoptosis of AECs, and subsequent lung fibrosis were notable in the RKT-treated mice. RKT administration increased the plasma ghrelin levels in wild-type mice, and it also mitigated the ALI response in both ghrelin-deficient mice and growth hormone secretagogue receptor-deficient mice after lung injury. Our results indicate that RKT administration exerts protective effects against ALI by protecting the AECs and regulating lung inflammation independently of the ghrelin system, and they highlight RKT as a promising therapeutic agent for the management of this intractable disease.

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Bleomycin-induced nuclear factor-κB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3β

Cited by 17 publications

References 30 publications

GSK-3 as potential target for therapeutic intervention in cancer

GSK-3 as potential target for therapeutic intervention in cancer

The Role of Glycogen Synthase Kinase 3-β in Immunity and Cell Cycle: Implications in Esophageal Cancer

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner

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