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The UVB-Stimulated Expression of Transglutaminase 1 Is Mediated Predominantly via the NFκB Signaling Pathway: New Evidence of Its Significant Attenuation through the Specific Interruption of the p38/MSK1/NFκBp65 Ser276 Axis.

Terazawa S, Mori S, Nakajima H, Yasuda M, Imokawa G - PLoS ONE (2015)

Bottom Line: Treatment with astaxanthin immediately after UVB irradiation did not attenuate the increased phosphorylation of Ser536/Ser468NFκBp65, c-Jun, ATK-2 and CK2, and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or I-κBα, respectively.However, the same treatment with astaxanthin significantly abolished the UVB-stimulated expression of TGase 1 protein, which was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1, Ser276NFκBp65 and Ser133CREB.The MSK1 inhibitor H89 significantly down-regulated the increased protein expression of TGase 1 in UVB-exposed human keratinocytes, which was accompanied by an abrogating effect on the increased phosphorylation of Ser276NFκBp65 and Ser133CREB but not Thr565/Ser376/Ser360MSK1.

View Article: PubMed Central - PubMed

Affiliation: Research Institute for Biological Functions, Chubu University, Aichi, Japan.

ABSTRACT
The influence of ultraviolet B (UVB) radiation on transglutaminase 1 (TGase 1), a major factor that regulates skin keratinization, has not been sufficiently characterized especially at the gene or protein level. Thus, we determined whether UVB affects the expression of TGase 1 in human keratinocytes and clarified the intracellular stress signaling mechanism(s) involved. Exposure of human keratinocytes to UVB significantly up-regulated the expression of TGase 1 at the gene and protein levels. Treatment with inhibitors of p38, MEK, JNK or NFκB significantly abolished the UVB-stimulated protein expression of TGase 1. Treatment with astaxanthin immediately after UVB irradiation did not attenuate the increased phosphorylation of Ser536/Ser468NFκBp65, c-Jun, ATK-2 and CK2, and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or I-κBα, respectively. However, the same treatment with astaxanthin significantly abolished the UVB-stimulated expression of TGase 1 protein, which was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1, Ser276NFκBp65 and Ser133CREB. The MSK1 inhibitor H89 significantly down-regulated the increased protein expression of TGase 1 in UVB-exposed human keratinocytes, which was accompanied by an abrogating effect on the increased phosphorylation of Ser276NFκBp65 and Ser133CREB but not Thr565/Ser376/Ser360MSK1. Transfection of human keratinocytes with MSK1 siRNA suppressed the UVB-stimulated protein expression of TGase 1. These findings suggest that the UVB-stimulated expression of TGase 1 is mediated predominantly via the NFκB pathway and can be attenuated through a specific interruption of the p38/MSK1/NFκBp65Ser276 axis.

No MeSH data available.


Related in: MedlinePlus

Effects of UVB radiation on the gene and protein expression levels of TGase 1.HPKs were exposed to UVB at a dose of 80 mJ/cm2 and were cultured for 24 and 48 h and then analyzed by real-time RT-PCR and Western blotting, respectively. (A) The gene expression level. RT-PCR results are normalized to GAPDH; values are means ± S.D. derived from 3 independent experiments. **: p<0.01. (B) The protein expression level. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. derived from 3 independent experiments. **: p<0.01.
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pone.0136311.g001: Effects of UVB radiation on the gene and protein expression levels of TGase 1.HPKs were exposed to UVB at a dose of 80 mJ/cm2 and were cultured for 24 and 48 h and then analyzed by real-time RT-PCR and Western blotting, respectively. (A) The gene expression level. RT-PCR results are normalized to GAPDH; values are means ± S.D. derived from 3 independent experiments. **: p<0.01. (B) The protein expression level. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. derived from 3 independent experiments. **: p<0.01.

Mentions: We first examined the gene and protein expression levels of TGase 1 in HPKs after a single UVB exposure at a dose of 80 mJ/cm2. UVB induced a significant increase of TGase 1 at 24 and 48 h post-irradiation at the gene and protein levels, respectively (Fig 1).


The UVB-Stimulated Expression of Transglutaminase 1 Is Mediated Predominantly via the NFκB Signaling Pathway: New Evidence of Its Significant Attenuation through the Specific Interruption of the p38/MSK1/NFκBp65 Ser276 Axis.

Terazawa S, Mori S, Nakajima H, Yasuda M, Imokawa G - PLoS ONE (2015)

Effects of UVB radiation on the gene and protein expression levels of TGase 1.HPKs were exposed to UVB at a dose of 80 mJ/cm2 and were cultured for 24 and 48 h and then analyzed by real-time RT-PCR and Western blotting, respectively. (A) The gene expression level. RT-PCR results are normalized to GAPDH; values are means ± S.D. derived from 3 independent experiments. **: p<0.01. (B) The protein expression level. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. derived from 3 independent experiments. **: p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549294&req=5

pone.0136311.g001: Effects of UVB radiation on the gene and protein expression levels of TGase 1.HPKs were exposed to UVB at a dose of 80 mJ/cm2 and were cultured for 24 and 48 h and then analyzed by real-time RT-PCR and Western blotting, respectively. (A) The gene expression level. RT-PCR results are normalized to GAPDH; values are means ± S.D. derived from 3 independent experiments. **: p<0.01. (B) The protein expression level. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. derived from 3 independent experiments. **: p<0.01.
Mentions: We first examined the gene and protein expression levels of TGase 1 in HPKs after a single UVB exposure at a dose of 80 mJ/cm2. UVB induced a significant increase of TGase 1 at 24 and 48 h post-irradiation at the gene and protein levels, respectively (Fig 1).

Bottom Line: Treatment with astaxanthin immediately after UVB irradiation did not attenuate the increased phosphorylation of Ser536/Ser468NFκBp65, c-Jun, ATK-2 and CK2, and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or I-κBα, respectively.However, the same treatment with astaxanthin significantly abolished the UVB-stimulated expression of TGase 1 protein, which was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1, Ser276NFκBp65 and Ser133CREB.The MSK1 inhibitor H89 significantly down-regulated the increased protein expression of TGase 1 in UVB-exposed human keratinocytes, which was accompanied by an abrogating effect on the increased phosphorylation of Ser276NFκBp65 and Ser133CREB but not Thr565/Ser376/Ser360MSK1.

View Article: PubMed Central - PubMed

Affiliation: Research Institute for Biological Functions, Chubu University, Aichi, Japan.

ABSTRACT
The influence of ultraviolet B (UVB) radiation on transglutaminase 1 (TGase 1), a major factor that regulates skin keratinization, has not been sufficiently characterized especially at the gene or protein level. Thus, we determined whether UVB affects the expression of TGase 1 in human keratinocytes and clarified the intracellular stress signaling mechanism(s) involved. Exposure of human keratinocytes to UVB significantly up-regulated the expression of TGase 1 at the gene and protein levels. Treatment with inhibitors of p38, MEK, JNK or NFκB significantly abolished the UVB-stimulated protein expression of TGase 1. Treatment with astaxanthin immediately after UVB irradiation did not attenuate the increased phosphorylation of Ser536/Ser468NFκBp65, c-Jun, ATK-2 and CK2, and did not abrogate the increased or diminished protein levels of c-Jun/c-Fos or I-κBα, respectively. However, the same treatment with astaxanthin significantly abolished the UVB-stimulated expression of TGase 1 protein, which was accompanied by the attenuated phosphorylation of Thr565/Ser376/Ser360MSK1, Ser276NFκBp65 and Ser133CREB. The MSK1 inhibitor H89 significantly down-regulated the increased protein expression of TGase 1 in UVB-exposed human keratinocytes, which was accompanied by an abrogating effect on the increased phosphorylation of Ser276NFκBp65 and Ser133CREB but not Thr565/Ser376/Ser360MSK1. Transfection of human keratinocytes with MSK1 siRNA suppressed the UVB-stimulated protein expression of TGase 1. These findings suggest that the UVB-stimulated expression of TGase 1 is mediated predominantly via the NFκB pathway and can be attenuated through a specific interruption of the p38/MSK1/NFκBp65Ser276 axis.

No MeSH data available.


Related in: MedlinePlus