Etelcalcetide decreases the PTH-calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism.

Introduction: Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion.

Materials And Methods: The PTH-calcium setpoint and maximum and minimum PTH secretion were determined using an 'in vivo setpoint analyses.' The PTH-calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups.

Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells.

Introduction: Etelcalcetide (Parsabiv, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown.

Pharmacology of Parsabiv (etelcalcetide, ONO-5163/AMG 416), a novel allosteric modulator of the calcium-sensing receptor, for secondary hyperparathyroidism in hemodialysis patients.

Etelcalcetide hydrochloride (Parsabiv, ONO-5163/AMG 416) is an allosteric modulator of the calcium (Ca)-sensing receptor that was originally produced by KAI Pharmaceuticals Inc. (now Amgen Inc.).

[The Discovery, Research and Development of Etelcalcetide Hydrochloride, the World 1st Intravenous Calcimimetics.].

Etelcalcetide hydrochloride is the first intravenous calcimimetics agent for secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is to be administered through dialysis circuit by physician or medical staff upon completion of dialysis and such administration is expected to reduce the burden of medication in patients. From the nonclinical study results, etelcalcetide functions as an allosteric activator of calcium-sensing receptor(CaSR).

Role of calnexin in the ER quality control and productive folding of CFTR; differential effect of calnexin knockout on wild-type and DeltaF508 CFTR.

Cystic fibrosis (CF) is caused by the mutation in CF transmembrane conductance regulator (CFTR), a cAMP-dependent Cl(-) channel at the plasma membrane of epithelium. The most common mutant, DeltaF508 CFTR, has competent Cl(-) channel function, but fails to express at the plasma membrane since it is retained in the endoplasmic reticulum (ER) by the ER quality control system. Here, we show that calnexin (CNX) is not necessary for the ER retention of DeltaF508 CFTR.

Phosphatidic acid metabolism regulates the intracellular trafficking and retrotranslocation of CFTR.

The cystic fibrosis transmembrane conductance regulator (CFTR) is transported to the plasma membrane from endoplasmic reticulum (ER) through the Golgi. Crucial to these trafficking events is the role of not only the proteinous factors but also the membrane lipids. However, the involvement of lipids, such as phospholipids, on the regulation of CFTR trafficking has been largely unexplored.

The bacterium, nontypeable Haemophilus influenzae, enhances host antiviral response by inducing Toll-like receptor 7 expression: evidence for negative regulation of host anti-viral response by CYLD.

The incidence of mixed viral/bacterial infections has increased recently because of the dramatic increase in antibiotic-resistant strains, the emergence of new pathogens, and the resurgence of old ones. Despite the relatively well-known role of viruses in enhancing bacterial infections, the impact of bacterial infections on viral infections remains unknown. In this study, we provide direct evidence that nontypeable Haemophilus influenzae (NTHi), a major respiratory bacterial pathogen, augments the host antiviral response by up-regulating epithelial Toll-like receptor 7 (TLR7) expression in vitro and in vivo.

Curcumin enhances cystic fibrosis transmembrane regulator expression by down-regulating calreticulin.

Curcumin has been reported to correct cystic fibrosis caused by the DeltaF508 mutation of the cystic fibrosis transmembrane regulator (CFTR) but its mechanistic action remains unclear. We have recently demonstrated that the ER chaperone calreticulin (CRT) negatively regulates the CFTR cell surface expression and activity. Thus, we aimed at determining whether CRT mediates the effect of curcumin on CFTR.

Bafilomycin A1-sensitive pathway is required for the maturation of cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasians caused by the trafficking defects of CF transmembrane conductance regulator (CFTR), which is a cAMP-dependent Cl- channel at the plasma membrane. The trafficking pathway of CFTR is thought to be non-conventional because CFTR maturation is inhibited by the dysfunction of syntaxin 13, which is involved in protein recycling via endosomal pathway. In this study, to clarify whether the endosomal trafficking is required for CFTR maturation, we utilized a specific vacuolar H+-ATPase inhibitor, bafilomycin A1 (BafA1), which inhibits the protein trafficking from early endosome.

Calreticulin facilitates the cell surface expression of ABCG5/G8.

ATP-binding cassette (ABC) G5 (G5) and ABCG8 (G8) heterodimerize and function as sterol transporter that promote biliary excretion of neutral sterols. Both G5 and G8 interact with a lectin-like chaperone, calnexin (CNX), in the endoplasmic reticulum (ER) but the significance of this interaction remains unclear. Here, we show that not only CNX, but also its homologue calreticulin (CRT), is involved in the biosynthesis of G5/G8 sterol transporter.

Calreticulin negatively regulates the cell surface expression of cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent Cl- channel at the plasma membrane, and its malfunction results in cystic fibrosis, the most common lethal genetic disease in Caucasians. Quality control of CFTR is strictly regulated by several molecular chaperones. Here we show that calreticulin (CRT), which is a lectin-like chaperone in the endoplasmic reticulum (ER), negatively regulates the cell surface CFTR.

Characterization of the trafficking pathway of cystic fibrosis transmembrane conductance regulator in baby hamster kidney cells.

To examine the unknown trafficking pathway of the cystic fibrosis transmembrane conductance regulator (CFTR) from the endoplasmic reticulum (ER), we utilized baby hamster kidney cells stably expressing CFTR fused with green fluorescent protein. CFTR trafficking from the ER was visualized and analyzed by immunocytochemical analyses. Here we show that CFTR was exported from the ER to the cis-Golgi and early endosome, suggesting that CFTR transport in the early secretory pathway may utilize a non-conventional pathway.

Delta F508 CFTR pool in the endoplasmic reticulum is increased by calnexin overexpression.

The most common cystic fibrosis transmembrane conductance regulator (CFTR) mutant in cystic fibrosis patients, Delta F508 CFTR, is retained in the endoplasmic reticulum (ER) and is consequently degraded by the ubiquitin-proteasome pathway known as ER-associated degradation (ERAD). Because the prolonged interaction of Delta F508 CFTR with calnexin, an ER chaperone, results in the ERAD of Delta F508 CFTR, calnexin seems to lead it to the ERAD pathway. However, the role of calnexin in the ERAD is controversial.

Calnexin Delta 185-520 partially reverses the misprocessing of the Delta F508 cystic fibrosis transmembrane conductance regulator.

Abnormal retention of Delta F508 CFTR (cystic fibrosis transmembrane conductance regulator) in the endoplasmic reticulum is a major cause of cystic fibrosis (CF). We show that calnexin Delta 185-520 but not calnexin can partially reverse the mislocalization of Delta F508 CFTR. This 256-amino acid protein has neither the transmembrane domain nor the P domain of calnexin.