The Role of Constitutive Nitric-oxide Synthase in Ultraviolet B Light-induced Nuclear Factor κB Activity

Tong, Lingying; Wu, Shiyong

doi:10.1074/jbc.m114.600023

Cited by 17 publications

(19 citation statements)

References 45 publications

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“…While UVB increased the expression of Bag‐1/S (Figure B, Lanes 2 vs. 1; 6 vs. 5; Table ), it reduced the expression of Bag‐1/S in the cells treated with S3I‐201 (Figure B, Lanes 4 vs. 3; 8 vs. 7; Table ), suggesting there are other mechanism(s) that also downregulate Bag‐1/S expression post‐UVB. Given that Stat3 mainly functions as a transcription activator , it is possible that the expression of Bag‐1/S is regulated by the phosphorylation of Stat3 through transcription regulation and by phosphorylation of eIF2α through translation regulation as we previously reported . Our results further indicated that the CIRP‐p‐Stat3 cascade‐upregulated expression of Bag‐1/S protects the cells from UVB‐induced PARP cleavage and caspase‐3 activation (Figures and ), which agrees with previous reports indicating Bag‐1/S is associated with stress resistance and anti‐apoptosis .…”

Section: Discussionsupporting

confidence: 92%

“…In this study, we demonstrated for the first time that CIRP expression is elevated in all tested skin cancer cell lines including melanoma and non‐melanoma cells (Figure ); as well as in keratinocytes exposed to a relatively low dose of UVB (3–5 mJ/cm 2 ) acutely or chronically (Figures and ). In opposite, the higher dose of UVB (50 mJ/cm 2 ) reduced the expression of CIRP, which could be due to the inhibition of translation of the protein as we previously reported . The potential role of CIRP in UVB‐induced skin carcinogenesis was further indicated by its function in regulation of Tyr‐705 phosphorylation of Stat3 and the expression of its downstream genes—cyclin D1 and VEGF (Figure ), two factors that are well known for their roles in promoting oncogenic cell growth and survival .…”

Section: Discussionmentioning

confidence: 60%

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The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation

Liao

Feng

Zhang

et al. 2017

Molecular Carcinogenesis

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UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3 in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm 2 ), but not high dose (50 mJ/cm 2 ), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation. We also demonstrated that CIRP expression is required for the low dose UVB-induced Tyr705-phosphorylation, but not total amount, of Stat3. The p-Stat3 level is correlated with the expression levels of cyclin D1 and VEGF, two known downstream cell growth regulators of Stat3, as well as Bag-1/S, an apoptosis regulator. Inhibition of Stat3 DNA-binding activity by S3I-201 leads to a reduction of the p-Stat3 and Bag-1/S along with growth and survival of keratinocytes post-UVB; and the effect of S3I-201 on the UVB-irradiated cells can be partially inhibited by overexpression of CIRP or Bag-1/S. Furthermore, the overexpression of Bag-1/S can totally inhibit UVBinduced PARP cleavage and caspase 3 activation. The results presented above led us to propose that CIRP-p(705)Stat3 cascade promotes cell proliferation and survival post-UVB via upregulating the expression of cyclin D1 and Bag-1/S, respectively. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 60%

The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation

Liao

Feng

Zhang

et al. 2017

Molecular Carcinogenesis

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“…International Publisher from L-arginine. There are three isoforms of NOS: neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), which have differences in their distribution, regulation and the ability to produce NO [15][16][17][18][19][20]. Both nNOS and eNOS belong to constitutive NOS (cNOS).…”

Section: Ivyspringmentioning

confidence: 99%

PM2.5 exposure induces vascular dysfunction via NO generated by iNOS in lung of ApoE-/- mouse

Long¹,

Zhu²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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PM2.5 exposure exacerbates cardiovascular diseases via oxidative stress and inflammation, the detailed mechanism of which is unclear. In this study, the effects of oxidative stress and inflammation, as well as vascular structure and function were studied by multiple PM2.5 exposure model of ApoE-/-mice. The results indicated that NO produced by iNOS not cNOS might play important roles in inducing vascular dysfunction after PM2.5 exposure. The occurrence order and causality among NO, other oxidative stress indicators and inflammation is explored by single PM2.5 exposure. The results showed that NO generated by iNOS occurred earlier than that of other oxidative stress indicators, which was followed by the increased inflammation. Inhibition of NOS could effectively block the raise of NO, oxidative stress and inflammation after PM2.5 exposure. All in all, we firstly confirmed that NO was the initiation factor of PM2.5 exposure-induced oxidative stress, which led to inflammation and the following vascular dysfunction.

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“…16,17 However, NO generated from constitutive NOS isoforms has also been shown to activate NF-kB. 18 The pro-apoptotic or tumor suppressor gene p53 plays an important role in the cellular response to DNA damage induced by chemical and physical mutagens. The exposure of human cells to NO generated from an NO donor or NOS-2 overexpression results in p53 protein accumulation.…”

Section: Introductionmentioning

confidence: 99%

Antitumoral gene-based strategy involving nitric oxide synthase type III overexpression in hepatocellular carcinoma

et al. 2015

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Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

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The Role of Constitutive Nitric-oxide Synthase in Ultraviolet B Light-induced Nuclear Factor κB Activity

Cited by 17 publications

References 45 publications

The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation

The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation

PM2.5 exposure induces vascular dysfunction via NO generated by iNOS in lung of ApoE-/- mouse

Antitumoral gene-based strategy involving nitric oxide synthase type III overexpression in hepatocellular carcinoma

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