PTH-C1: a rat continuous cell line expressing the parathyroid phenotype

Fabbri, Sergio; Ciuffi, Simone; Nardone, Valeria; Gomes, Ana Rita; Mavilia, Carmelo; Zonefrati, Roberto; Galli, Gianna; Luzi, Ettore; Tanini, Annalisa; Brandi, Maria Luisa

doi:10.1007/s12020-014-0229-7

Cited by 15 publications

(13 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4a , 4d ), nor did Ca 2+ affect G-protein activation via GABA B1 R when each receptor was expressed alone in HEK-293 cells. Similar inhibitory action of baclofen on Ca 2+ -mediated Gq activation were obtained in rat parathyroid-derived PTH-C1 cells 34 ( Extended Data Fig. 5a ) with (left panel) or without (right panel) supplementation of exogenous CaSR and GABA B1 R cDNAs.…”

Section: Resultssupporting

confidence: 72%

PTH hypersecretion triggered by a GABAB1 and Ca2+-sensing receptor heterocomplex in hyperparathyroidism

Chang

Jean-Alphonse

et al. 2020

Nat Metab

View full text Add to dashboard Cite

Molecular mechanisms mediating tonic secretion of parathyroid hormone (PTH) in response to hypocalcemia and hyperparathyroidism (HPT) are unclear. Here we demonstrate increased heterocomplex formation between the calcium-sensing receptor (CaSR) and metabotropic GABA B1 receptor (GABA B1 R) in hyperplastic parathyroid glands (PTGs) of patients with primary and secondary HPT. Targeted ablation of GABA B1 R or glutamic acid decarboxylase 1 and 2 in PTGs produces hypocalcemia and hypoparathyroidism and prevents PTH hypersecretion in PTGs cultured from mouse models of hereditary HPT and dietary calcium-deficiency. Co-binding of CaSR/GABA B1 R complex by baclofen and high extracellular calcium blocks the coupling of heterotrimeric G-proteins to homomeric CaSRs in cultured cells and promotes PTH secretion in cultured mouse PTGs. These results combined with the ability of PTG to synthesize GABA support a critical autocrine action of GABA/GABA B1 R in mediating tonic PTH secretion of PTGs and ascribe aberrant activities of CaSR/GABA B1 R heteromer to HPT.

show abstract

Section: Resultssupporting

confidence: 72%

PTH hypersecretion triggered by a GABAB1 and Ca2+-sensing receptor heterocomplex in hyperparathyroidism

Chang

Jean-Alphonse

et al. 2020

Nat Metab

View full text Add to dashboard Cite

show abstract

“…The rat parathyroid epithelial cell line PTH-C1 has been described elsewhere (17). Cells were seeded into 24-well plates in Ham's F-12 Coon's Modification Medium (Sigma-Aldrich) containing 10% FCS, 100 U/ml penicillin G, and 100 mg/ml streptomycin sulfate.…”

Section: Pth Elisasmentioning

confidence: 99%

Calcium-Sensing Receptor Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1: Epitopes, Specificity, Functional Affinity, IgG Subclass, and Effects on Receptor Activity

Habibullah

Porter

Kluger

et al. 2018

The Journal of Immunology

View full text Add to dashboard Cite

A major manifestation of autoimmune polyendocrine syndrome type 1 (APS1) is hypoparathyroidism, which is suggested to result from aberrant immune responses against the parathyroid glands. The calcium-sensing receptor (CaSR), which plays a pivotal role in maintaining calcium homeostasis by sensing blood calcium levels and regulating release of parathyroid hormone (PTH), is an autoantibody target in APS1. In this study, the aim was to characterize the binding sites, specificity, functional affinity, IgG subclass, and functional effects of CaSR autoantibodies using phage-display technology, ELISA, and bioassays. The results indicated that CaSR autoantibody binding sites were at aa 41-69, 114-126, 171-195, and 260-340 in the extracellular domain of the receptor. Autoantibodies against CaSR epitopes 41-69, 171-195, and 260-340 were exclusively of the IgG1 subclass. Autoantibody responses against CaSR epitope 114-126 were predominantly of the IgG1 with a minority of the IgG3 subclass. Only autoantibodies recognizing CaSR epitopes 114-126 and 171-195 affected receptor activity; inositol-phosphate accumulation was increased significantly in HEK293-CaSR cells, and PTH secretion from PTH-C1 cells was reduced significantly when either were incubated with purified Ab and Ca 2+ compared with Ca 2+ alone. In conclusion, although the majority of APS1 patients do not have CaSR-stimulating autoantibodies, the hypoparathyroid state in a small minority of patients is the result of functional suppression of the parathyroid glands.

show abstract

“…Parathyroid cells depleted of TRPC1 secrete more PTH. Derived from rat PTG, PTH-C1 cells express CaSR, produce and secrete PTH, and are currently the only known cell line available for studying PTH secretion in rodents (26). Using CRISPR/Cas9 gene editing, we introduced a frameshift in the Trpc1 locus in PTH-C1 cells and generated several stable clones.…”

Section: Resultsmentioning

confidence: 99%

“…PTH-C1 cells, a cell line derived from rat PTG, were a gift from Maria Luisa Brandi (FirmoLab, Università degli Studi di Firenze) and cultured in prescribed conditions (26). HEK293 and HEK293T cells were purchased from ATCC and cultured in DMEM (Corning; 10-013) enriched by 10% FBS (Atlanta Biologicals; S11550).…”

Section: Cell Culturementioning

confidence: 99%