Molecular Signaling and Transcriptional Regulation of Histamine H1 Receptor Gene.

Abstract

Histamine-activated histamine H1 receptor (H1R) signaling regulates many gene expressions, mainly through the protein kinase C (PKC)/extracellular signal-regulated kinases (ERK) signaling. Involvement of other signaling, including NF-κB, Wnt, RUNX-2, and Rho A signaling was also demonstrated. In addition, cAMP production through the activation of H1R signaling was reported. H1R gene itself is also up-regulated by the activation of H1R signaling with histamine. Here, we review our recent findings in the molecular signaling and transcriptional regulation of the H1R gene. Stimulation with histamine up-regulates H1R gene expression through the activation of H1R in HeLa cells. The PKCδ/ERK/poly(ADP)ribosyl transferase-1 (PARP-1) signaling was involved in this up-regulation. Heat shock protein 90 also plays an important role in regulating PKCδ translocation. Promoter analyses revealed the existence of two promoters in the human H1R gene in HeLa cells. H1R-activated H1R gene up-regulation in response to histamine was also observed in U373 astroglioma cells. However, this up-regulation was mediated not through the PKCδ signaling but possibly through the PKCα signaling. In addition, the promoter region responsible for histamine-induced H1R gene transcription in U373 cells was different from that of HeLa cells. These findings suggest that the molecular signaling and transcriptional regulation of the H1R gene are different between neuronal cells and non-neuronal cells.