Because an acidic cellular microenvironment is engendered by inflammation and may determine cell differentiation, we elucidated the impact of acidic conditions on induction of proopiomelanocortin (POMC) expression. Here, we demonstrate mechanisms for proton sensitivity of CRH receptor 1 (CRHR1) signaling to POMC and ACTH production. Low pH (6.8) resulted in doubling of POMC expression and ACTH production in pituitary cell line AtT-20 and in primary mouse pituitary cells. Using CRISPR knockout, we show that CRHR1 is necessary for acid-induced POMC expression, and this induction is mediated by CRHR1 histidine residues and calmodulin-dependent protein kinase II in both pituitary corticotroph cells and in nonpituitary cell lines expressing ectopic ACTH. In contrast, CRH ligand binding affinity to CRHR1 was decreased with acidic pH, implying that proton-induced POMC expression prevails in acidic conditions independently of CRH ligand binding. The results indicate that proton-induced CRHR1 signaling regulates ACTH production in response to an acidic microenvironment.
Pubmed ID: 30535142 RIS Download
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This polyclonal targets CRHR1, CRHR2
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets NeuroD1
View all literature mentionsThis polyclonal targets NUR77
View all literature mentionsThis monoclonal targets ACTH
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis monoclonal targets CREB antibody [5G3]
View all literature mentionsThis unknown targets CaMKII
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets PITX1
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets POMC
View all literature mentionsThis polyclonal targets CRHR1 antibody produced in rabbit
View all literature mentionsCell line B16-F0 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line COLO 320DM is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AtT-20/D16v-F2 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line DMS 79 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis unknown targets CaMKII
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis polyclonal targets POMC
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsCell line B16-F0 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DMS 79 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line COLO 320DM is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AtT-20/D16v-F2 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThis monoclonal targets CREB antibody [5G3]
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets PITX1
View all literature mentionsThis polyclonal targets CRHR1 antibody produced in rabbit
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets NeuroD1
View all literature mentionsThis polyclonal targets NUR77
View all literature mentionsThis monoclonal targets ACTH
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