In Vivo and in Vitro Models of Demyelinating Disease. Possible Relationship between Induction of Regulatory Subunit from cAMP Dependent Protein Kinases and Inhibition of JHMV Replication in Cultured Oligodendrocytes

1990 ◽  
pp. 261-266 ◽  
Author(s):  
G. A. R. Wilson ◽  
D. V. Mohandas ◽  
S. Dales
Keyword(s):  
Protein Kinases ◽  
Demyelinating Disease ◽  
In Vitro Models ◽  
Regulatory Subunit ◽  
Dependent Protein

scholarly journals Celecoxib reduces glucocorticoids in vitro and in a mouse model with adrenocortical hyperplasia

2015 ◽  
Vol 23 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Sisi Liu ◽  
Emmanouil Saloustros ◽  
Annabel Berthon ◽  
Matthew F Starost ◽  
Isabelle Sahut-Barnola ◽  
...  
Keyword(s):  
Mouse Model ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Adrenocortical Cells ◽  
Gene Coding ◽  
Bilateral Adrenal Hyperplasia ◽  
Dependent Protein ◽  
And Control

Primary pigmented nodular adrenocortical disease (PPNAD), whether in the context of Carney complex (CNC) or isolated, leads to ACTH-independent Cushing's syndrome (CS). CNC and PPNAD are caused typically by inactivating mutations of PRKAR1A, a gene coding for the type 1a regulatory subunit (R1α) of cAMP-dependent protein kinase (PKA). Mice lacking Prkar1a, specifically in the adrenal cortex (AdKO) developed CS caused by bilateral adrenal hyperplasia (BAH), which is formed from the abnormal proliferation of fetal-like adrenocortical cells. Celecoxib is a cyclooxygenase 2 (COX2) inhibitor. In bone, Prkar1a inhibition is associated with COX2 activation and prostaglandin E2 (PGE2) production that, in turn, activates proliferation of bone stromal cells. We hypothesized that COX2 inhibition may have an effect in PPNAD. In vitro treatment of human cell lines, including one from a patient with PPNAD, with celecoxib resulted in decreased cell viability. We then treated AdKO and control mice with 1500 mg/kg celecoxib or vehicle. Celecoxib treatment led to decreased PGE2 and corticosterone levels, reduced proliferation and increased apoptosis of adrenocortical cells, and decreased steroidogenic gene expression. We conclude that, in vitro and in vivo, celecoxib led to decreased steroidogenesis. In a mouse model of PPNAD, celecoxib caused histological changes that, at least in part, reversed BAH and this was associated with a reduction of corticosterone levels.

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