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Clock Gene Modulation by TNF-α Depends on Calcium and p38 MAP Kinase Signaling
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Personen und Körperschaften: | , , , , |
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Titel: |
Clock Gene Modulation by TNF-α Depends on Calcium and p38 MAP Kinase Signaling |
In: | Journal of Biological Rhythms, 24, 2009, 4, S. 283-294 |
veröffentlicht: |
SAGE Publications
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Umfang: | 283-294 |
ISSN: |
0748-7304 1552-4531 |
DOI: | 10.1177/0748730409336579 |
Zusammenfassung: | <jats:p> A 24-h treatment with the cytokine tumor necrosis factor-α (TNF-α) suppresses transcription of E-box—driven clock genes (D-site albumin promoter binding protein, Dbp; Tyrotroph embryonic factor, Tef ; Hepatic leukemia factor, Hlf; Period homolog to Drosophila 1/2/3, Per1, Per2, and Per3) by yet unknown molecular mechanisms. The attenuation of clock genes has been suggested as a putative cause for the development of sickness behavior syndrome in infectious and autoimmune diseases. Here, the authors studied the effect of TNF-α at early time points (<3 h) on intracellular signaling events and clock gene expression in fibroblasts. Interaction of TNF-α with TNFR1 ( Tnfrsf1a , CD120a, p55), but not TNFR2 ( Tnfrsf1b, CD120b , p75), leads to fast downregulation of gene expression of Dbp and upregulation of negative regulators of the molecular clock, Per1 and Per2, Cryptochrome-1 ( Cry1), and Differentiated embryo chondrocytes-1 ( Dec1). Since the decrease of Dbp is also observed in cells deficient for Per1/Per2, Cry1/ Cry2 , or Dec1, these genes are unlikely to be responsible for inhibition of Dbp. The early effect of TNF-α on the clock gene Per1 is dependent on p38, mitogen-activated protein kinase (MAPK), and/or calcium signaling, whereas the effect on Dbp is independent of p38 MAPK, but also involves calcium signaling. Both genes remain unaffected by the NF-κB and AP-1 pathway. Taken collectively these data show p38 MAPK- and calcium-dependent TNFR1-mediated transient increase of the negative regulator Per1 and an independent decrease of Dbp. </jats:p> |
Format: | E-Article |
Quelle: | SAGE Publications (CrossRef) |
Sprache: | Englisch |