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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: 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.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.

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 irradiation on the Thr581/Ser360/Ser376 phosphorylation of MSK1 and the inhibitory effect of AX.(A) Thr581 phosphorylation of MSK1 in HPKs at 0.5 h post-irradiation. (B), (C) Ser360/ Ser376 phosphorylation of MSK1 in human HaCaT keratinocytes at 0.5 h post-irradiation. HPKs or human HaCaT keratinocytes were exposed to UVB irradiation at a dose of 80 mJ/cm2 immediately after which the cells were treated with AX at the indicated concentrations. Lysates were harvested at 30 min after UVB irradiation and were immunoblotted with antibodies to Thr581/Ser376/360 phosphorylated MSK1. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. from 3 independent experiments. *: p<0.05, **:p<0.01.
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pone.0136311.g010: Effects of UVB irradiation on the Thr581/Ser360/Ser376 phosphorylation of MSK1 and the inhibitory effect of AX.(A) Thr581 phosphorylation of MSK1 in HPKs at 0.5 h post-irradiation. (B), (C) Ser360/ Ser376 phosphorylation of MSK1 in human HaCaT keratinocytes at 0.5 h post-irradiation. HPKs or human HaCaT keratinocytes were exposed to UVB irradiation at a dose of 80 mJ/cm2 immediately after which the cells were treated with AX at the indicated concentrations. Lysates were harvested at 30 min after UVB irradiation and were immunoblotted with antibodies to Thr581/Ser376/360 phosphorylated MSK1. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. from 3 independent experiments. *: p<0.05, **:p<0.01.

Mentions: In the present study, we found for the first time that UVB exposure (80 mJ/cm2) of HPKs significantly stimulated the Thr581 phosphorylation of MSK1 at 0.5 h post-irradiation, which was significantly abrogated by treatment with AX at 4 or 8 μM following UVB irradiation (Fig 10A). In UVB-exposed human HaCaT keratinocytes, while the Ser360/Ser376 phosphorylation of MSK1 was remarkably increased at 0.5 h post-irradiation, the post-irradiation treatment with AX distinctly abrogated those increases (Fig 10B and 10C).


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 irradiation on the Thr581/Ser360/Ser376 phosphorylation of MSK1 and the inhibitory effect of AX.(A) Thr581 phosphorylation of MSK1 in HPKs at 0.5 h post-irradiation. (B), (C) Ser360/ Ser376 phosphorylation of MSK1 in human HaCaT keratinocytes at 0.5 h post-irradiation. HPKs or human HaCaT keratinocytes were exposed to UVB irradiation at a dose of 80 mJ/cm2 immediately after which the cells were treated with AX at the indicated concentrations. Lysates were harvested at 30 min after UVB irradiation and were immunoblotted with antibodies to Thr581/Ser376/360 phosphorylated MSK1. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. from 3 independent experiments. *: p<0.05, **:p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549294&req=5

pone.0136311.g010: Effects of UVB irradiation on the Thr581/Ser360/Ser376 phosphorylation of MSK1 and the inhibitory effect of AX.(A) Thr581 phosphorylation of MSK1 in HPKs at 0.5 h post-irradiation. (B), (C) Ser360/ Ser376 phosphorylation of MSK1 in human HaCaT keratinocytes at 0.5 h post-irradiation. HPKs or human HaCaT keratinocytes were exposed to UVB irradiation at a dose of 80 mJ/cm2 immediately after which the cells were treated with AX at the indicated concentrations. Lysates were harvested at 30 min after UVB irradiation and were immunoblotted with antibodies to Thr581/Ser376/360 phosphorylated MSK1. Representative immunoblots from 3 independent experiments are shown; values are means ± S.D. from 3 independent experiments. *: p<0.05, **:p<0.01.
Mentions: In the present study, we found for the first time that UVB exposure (80 mJ/cm2) of HPKs significantly stimulated the Thr581 phosphorylation of MSK1 at 0.5 h post-irradiation, which was significantly abrogated by treatment with AX at 4 or 8 μM following UVB irradiation (Fig 10A). In UVB-exposed human HaCaT keratinocytes, while the Ser360/Ser376 phosphorylation of MSK1 was remarkably increased at 0.5 h post-irradiation, the post-irradiation treatment with AX distinctly abrogated those increases (Fig 10B and 10C).

Bottom Line: 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.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.

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