Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0221002 (
primary hyperparathyroidism
)
4,921
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca
2+
]
o
). [Ca
2+
]
o
activates calcium-sensing receptor (CASR), which interacts with the scaffold protein
filamin A
(
FLNA
). The study aimed to investigate: (1) the
FLNA
expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on
FLNA
-mediated ERK phosphorylation in HEK293 cells. Full-length
FLNA
immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that
FLNA
localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus
FLNA
fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous
FLNA
reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement,
FLNA
mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with
primary hyperparathyroidism
severity could be detected and
FLNA
transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca
2+
]
o
in the absence of
FLNA
. In conclusion,
FLNA
is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of
FLNA
reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation.
FLNA
is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.
...
PMID:Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors. 2787 58
