title: 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.
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.
authors: Research Institute for Biological Functions, Chubu University, Aichi, Japan.
authors: Shuko
authors: S
authors: Terazawa
authors: School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
authors: Shingo
authors: S
authors: Mori
authors: School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
authors: Hiroaki
authors: H
authors: Nakajima
authors: School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
authors: Michitaka
authors: M
authors: Yasuda
authors: Research Institute for Biological Functions, Chubu University, Aichi, Japan.
authors: Genji
authors: G
authors: Imokawa
mesh_terms: D047390:Casein Kinase II / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000528:radiation effects*; D020868:Gene Silencing; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D013312:Stress, Physiological; D051996:Transcription Factor RelA / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; D011503:Transglutaminases; C105804:transglutaminase 1; D047390:Casein Kinase II; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048051:p38 Mitogen-Activated Protein Kinases