Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells
Histamine H<sub>1</sub> receptor (H1R) is one of the targets of histamine in the nervous system and the peripheral tissues. Protein kinase Cδ (PKCδ) signaling is involved in histamine-induced upregulation of H1R gene expression in HeLa cells. Histamine also upregulates H1R gene expressio...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/43/3/88 |
| _version_ | 1797505850575683584 |
|---|---|
| author | Hiroyuki Mizuguchi Yuko Miyamoto Takuma Terao Haruka Yoshida Wakana Kuroda Yoshiaki Kitamura Noriaki Takeda Hiroyuki Fukui |
| author_facet | Hiroyuki Mizuguchi Yuko Miyamoto Takuma Terao Haruka Yoshida Wakana Kuroda Yoshiaki Kitamura Noriaki Takeda Hiroyuki Fukui |
| author_sort | Hiroyuki Mizuguchi |
| collection | DOAJ |
| description | Histamine H<sub>1</sub> receptor (H1R) is one of the targets of histamine in the nervous system and the peripheral tissues. Protein kinase Cδ (PKCδ) signaling is involved in histamine-induced upregulation of H1R gene expression in HeLa cells. Histamine also upregulates H1R gene expression in U-373 MG cells. However, the molecular signaling of this upregulation is still unclear. Here, we investigated the molecular mechanism of histamine-induced H1R gene upregulation in U-373 MG cells. Histamine-induced H1R gene upregulation was inhibited by H1R antagonist <i>d</i>-chlorpheniramine, but not by ranitidine, ciproxifan, or JNJ77777120, and H2R, H3R, or H4R antagonists, respectively. Ro-31-8220 and Go6976 also suppressed this upregulation, however, the PKCδ selective inhibitor rottlerin and the PKCβ selective inhibitor Ly333531 did not. Time-course studies showed distinct kinetics of H1R gene upregulation in U-373 MG cells from that in HeLa cells. A promoter assay revealed that the promoter region responsible for H1R gene upregulation in U-373 MG cells was different from that of HeLa cells. These data suggest that the H1R-activated H1R gene expression signaling pathway in U-373 MG cells is different from that in HeLa cells, possibly by using different promoters. The involvement of PKCα also suggests that compounds that target PKCδ could work as peripheral type H1R-selective inhibitors without a sedative effect. |
| first_indexed | 2024-03-10T04:24:14Z |
| format | Article |
| id | doaj.art-c49e66bbf01d4a078f6aa83ae05b058a |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T04:24:14Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-c49e66bbf01d4a078f6aa83ae05b058a2023-11-23T07:43:28ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-09-014331243125410.3390/cimb43030088Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG CellsHiroyuki Mizuguchi0Yuko Miyamoto1Takuma Terao2Haruka Yoshida3Wakana Kuroda4Yoshiaki Kitamura5Noriaki Takeda6Hiroyuki Fukui7Laboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, JapanDepartment of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, JapanDepartment of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, JapanDepartment of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, JapanDepartment of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, JapanDepartment of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, JapanDepartment of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, JapanLaboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, JapanHistamine H<sub>1</sub> receptor (H1R) is one of the targets of histamine in the nervous system and the peripheral tissues. Protein kinase Cδ (PKCδ) signaling is involved in histamine-induced upregulation of H1R gene expression in HeLa cells. Histamine also upregulates H1R gene expression in U-373 MG cells. However, the molecular signaling of this upregulation is still unclear. Here, we investigated the molecular mechanism of histamine-induced H1R gene upregulation in U-373 MG cells. Histamine-induced H1R gene upregulation was inhibited by H1R antagonist <i>d</i>-chlorpheniramine, but not by ranitidine, ciproxifan, or JNJ77777120, and H2R, H3R, or H4R antagonists, respectively. Ro-31-8220 and Go6976 also suppressed this upregulation, however, the PKCδ selective inhibitor rottlerin and the PKCβ selective inhibitor Ly333531 did not. Time-course studies showed distinct kinetics of H1R gene upregulation in U-373 MG cells from that in HeLa cells. A promoter assay revealed that the promoter region responsible for H1R gene upregulation in U-373 MG cells was different from that of HeLa cells. These data suggest that the H1R-activated H1R gene expression signaling pathway in U-373 MG cells is different from that in HeLa cells, possibly by using different promoters. The involvement of PKCα also suggests that compounds that target PKCδ could work as peripheral type H1R-selective inhibitors without a sedative effect.https://www.mdpi.com/1467-3045/43/3/88gene upregulationhistaminehistamine H<sub>1</sub> receptorsplice valianttranscription regulation |
| spellingShingle | Hiroyuki Mizuguchi Yuko Miyamoto Takuma Terao Haruka Yoshida Wakana Kuroda Yoshiaki Kitamura Noriaki Takeda Hiroyuki Fukui Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells Current Issues in Molecular Biology gene upregulation histamine histamine H<sub>1</sub> receptor splice valiant transcription regulation |
| title | Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells |
| title_full | Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells |
| title_fullStr | Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells |
| title_full_unstemmed | Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells |
| title_short | Signaling Pathway of Histamine H<sub>1</sub> Receptor-Mediated Histamine H<sub>1</sub> Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells |
| title_sort | signaling pathway of histamine h sub 1 sub receptor mediated histamine h sub 1 sub receptor gene upregulation induced by histamine in u 373 mg cells |
| topic | gene upregulation histamine histamine H<sub>1</sub> receptor splice valiant transcription regulation |
| url | https://www.mdpi.com/1467-3045/43/3/88 |
| work_keys_str_mv | AT hiroyukimizuguchi signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT yukomiyamoto signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT takumaterao signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT harukayoshida signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT wakanakuroda signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT yoshiakikitamura signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT noriakitakeda signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells AT hiroyukifukui signalingpathwayofhistaminehsub1subreceptormediatedhistaminehsub1subreceptorgeneupregulationinducedbyhistamineinu373mgcells |