Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway

Ding, Min; Huang, Chuanshu; Lu, Yongju; Bowman, Linda; Castranova, Vince; Vallyathan, Val

doi:10.1152/ajplung.00053.2005

Cited by 17 publications

(6 citation statements)

References 42 publications

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“…With respect to PI3K signaling, PKCa, even at physiological concentrations, serves as an endogenous negative feedback inhibitor of insulin signaling through IRS1, PI3K, PKB, and PKCl to the glucose transport system in both skeletal muscles and adipocytes (39), which is in line with the decreased PI3K phosphorylation in response to GH in the patient's fibroblasts. Finally, PKCa increases phosphorylation of Raf-1 kinase, which leads to the activation of the ERK-MAPK cascade (40), which is consistent with the increased sensitivity to GH of MAPK phosphorylation. As mentioned before, activation of this cascade has been associated with GH insensitivity (11).…”

Section: Discussionsupporting

confidence: 75%

A mosaic de novo duplication of 17q21–25 is associated with GH insensitivity, disturbed in vitro CD28-mediated signaling, and decreased STAT5B, PI3K, and NF-κB activation

Mul

Wu²,

Paus³

et al. 2012

European Journal of Endocrinology

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Objective: The established causes of GH insensitivity include defects of the GH receptor and STAT5B. The latter condition is also characterized by severe immunodeficiency. A recent case with short stature, GH resistance, and immunodeficiency due to an IkB mutation suggests that the NF-kB pathway may interact with STAT5B signaling. Design: Here, we present a case of a short child with several congenital anomalies as well as GH insensitivity and mild immunodeficiency associated with a mosaic de novo duplication of chromosome 17q21-25, suggesting that overexpression of one of the duplicated genes may be implicated in GH resistance. Methods and results: In vitro studies on blood lymphocytes showed disturbed signaling of the CD28 pathway, involving NF-kB and related proteins. Functional studies on cultured skin fibroblasts revealed that NF-kB activation, PI3K activity, and STAT5 phosphorylation in response to GH were suppressed, while the sensitivity to GH in terms of MAPK phosphorylation was increased. An in silico analysis of the duplicated genes showed that MAP3K3 and PRKCA are associated with the NF-kB pathway. Baseline MAP3K3 expression in T-cell blasts (TCBs) was normal, but PRKCA expression in TCBs and fibroblasts was significantly higher than that in control cells. Conclusions: We conclude that the 17q21-25 duplication is associated with GH insensitivity and disturbed STAT5B, PI3K, and NF-kB signaling, possibly due to PRKCA mRNA overexpression.

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Section: Discussionsupporting

confidence: 75%

A mosaic de novo duplication of 17q21–25 is associated with GH insensitivity, disturbed in vitro CD28-mediated signaling, and decreased STAT5B, PI3K, and NF-κB activation

Mul

Wu²,

Paus³

et al. 2012

European Journal of Endocrinology

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“…However, rIL-2 significantly affected downstream modulators of TCR signaling [ 14 ] converging toward cytokine promoter domains. For instance, the phospholipase C (PLC)γ-dependent pathway [ 75 , 76 ]. activates three major classes of transcription factors: NFAT, NF- k B and AP-1.…”

Section: Resultsmentioning

confidence: 99%

Molecular signatures induced by interleukin-2 on peripheral blood mononuclear cells and T cell subsets

et al. 2006

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Experimentally, interleukin-2 (IL-2) exerts complex immunological functions promoting the proliferation, survival and activation of T cells on one hand and inducing immune regulatory mechanisms on the other. This complexity results from a cross talk among immune cells which sways the effects of IL-2 according to the experimental or clinical condition tested. Recombinant IL-2 (rIL-2) stimulation of peripheral blood mononuclear cells (PBMC) from 47 donors of different genetic background induced generalized T cell activation and anti-apoptotic effects. Most effects were dependent upon interactions among immune cells. Specialized functions of CD4 and CD8 T cells were less dependent upon and often dampened by the presence of other PBMC populations. In particular, cytotoxic T cell effector function was variably affected with a component strictly dependent upon the direct stimulation of CD8 T cells in the absence of other PBMC. This observation may provide a roadmap for the interpretation of the discrepant biological activities of rIL-2 observed in distinct pathological conditions or treatment modalities.

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“…In the central nervous system, MMP-9 is involved in numerous pathophysiological responses, such as ECM degradation, tissue remodeling, neurite outgrowth, and injury repair [44]. Moreover, upregulation of MMP-9 may be implicated in the pathological processes of brain disorders, including stroke, AD, multiple sclerosis, and malignant glioma [72]. These findings of galangin inhibiting the thrombin-induced MMP-9 expression in SK-N-SH cells indicate that galangin might be a potential candidate for the therapeutic agents of brain inflammatory and degenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation

Yang

Lin

Hsiao

et al. 2018

IJMS

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Galangin, a member of the flavonol compounds of the flavonoids, could exert anti-inflammatory effects in various cell types. It has been used for the treatment of arthritis, airway inflammation, stroke, and cognitive impairment. Thrombin, one of the regulators of matrix metalloproteinase (MMPs), has been known as a vital factor of physiological and pathological processes, including cell migration, the blood–brain barrier breakdown, brain edema formation, neuroinflammation, and neuronal death. MMP-9 especially may contribute to neurodegenerative diseases. However, the effect of galangin in combating thrombin-induced MMP-9 expression is not well understood in neurons. Therefore, we attempted to explore the molecular mechanisms by which galangin inhibited MMP-9 expression and cell migration induced by thrombin in SK-N-SH cells (a human neuroblastoma cell line). Gelatin zymography, western blot, real-time PCR, and cell migration assay were used to elucidate the inhibitory effects of galangin on the thrmbin-mediated responses. The results showed that galangin markedly attenuated the thrombin-stimulated phosphorylation of proto-oncogene tyrosine-protein kinase (c-Src), proline-rich tyrosine kinase 2 (Pyk2), protein kinase C (PKC)α/β/δ, protein kinase B (Akt), mammalian target of rapamycin (mTOR), p42/p44 mitogen-activated protein kinase (MAPK), Jun amino-terminal kinases (JNK)1/2, p38 MAPK, forkhead box protein O1 (FoxO1), p65, and c-Jun and suppressed MMP-9 expression and cell migration in SK-N-SH cells. Our results concluded that galangin blocked the thrombin-induced MMP-9 expression in SK-N-SH cells via inhibiting c-Src, Pyk2, PKCα/βII/δ, Akt, mTOR, p42/p44 MAPK, JNK1/2, p38 MAPK, FoxO1, c-Jun, and p65 phosphorylation and ultimately attenuated cell migration. Therefore, galangin may be a potential candidate for the management of brain inflammatory diseases.

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Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway

Cited by 17 publications

References 42 publications

A mosaic de novo duplication of 17q21–25 is associated with GH insensitivity, disturbed in vitro CD28-mediated signaling, and decreased STAT5B, PI3K, and NF-κB activation

A mosaic de novo duplication of 17q21–25 is associated with GH insensitivity, disturbed in vitro CD28-mediated signaling, and decreased STAT5B, PI3K, and NF-κB activation

Molecular signatures induced by interleukin-2 on peripheral blood mononuclear cells and T cell subsets

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation

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