PubMed · 14362680
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
R DEBRE, P SOULIE. 1955. Introduction.. https://pubmed.ncbi.nlm.nih.gov/14362680/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Syncollin is a 13 kDa protein that is highly expressed in the exocrine pancreas. Syncollin normally exists as a doughnut-shaped homo-oligomer (quite probably a hexamer) in close association with the luminal surface of the zymogen granule membrane. In the present study, we examine the effect of expression of syncollin in AtT-20 neuroendocrine cells, which do not normally express this protein. Efficient expression was achieved by infection of the cells with adenoviral constructs encoding either untagged or GFP (green fluorescent protein)-tagged syncollin. Both forms of the protein were sorted into corticotropin (ACTH)-positive secretory vesicles present mainly at the tips of cell processes. Neither form affected basal corticotropin secretion or the constitutive secretion of exogenously expressed secreted alkaline phosphatase. In contrast, regulated secretion of corticotropin was inhibited (by 49%) by untagged but not by GFP-tagged syncollin. In parallel, untagged syncollin caused a 46% reduction in the number of secretory vesicles present at the tips of the cell processes. Syncollin-GFP was without effect. We could also show that native syncollin purified from rat pancreas was capable of permeabilizing erythrocytes. We suggest that syncollin may induce uncontrolled permeabilization of corticotropin-containing vesicles and subsequently destabilize them. Both forms of syncollin were tightly membrane-associated and appeared to exist as homooligomers. Hence, the lack of effect of syncollin-GFP on regulated exocytosis suggests that the GFP tag interferes in a subtler manner with the properties of the assembled protein.
BACKGROUND: Two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior were used to identify neurobiological correlates of trait anxiety. METHODS: We used Fos expression for mapping of neuronal activation patterns in response to mild anxiety-provoking challenges. RESULTS: In both lines, exposure to an open field (OF) or the open arm (OA) of an elevated plus-maze induced Fos expression in several brain areas of the anxiety/fear circuitry. Rats of the HAB type, which showed signs of a hyperanxious phenotype and a hyperreactive hypothalamic-pituitary-adrenal axis compared with LAB rats, exhibited a higher number of Fos-positive cells in the paraventricular nucleus of the hypothalamus, the lateral and anterior hypothalamic area, and the medial preoptic area in response to both OA and OF. Less Fos expression was induced in the cingulate cortex in HAB than in LAB rats. Differential Fos expression in response to either OA or OF was observed in few brain regions, including the thalamus and hippocampus. CONCLUSIONS: The present data indicate that the divergent anxiety-related behavioral response of HAB versus LAB rats to OF and OA exposures is associated with differential neuronal activation in restricted parts of the anxiety/fear circuitry. Distinct hypothalamic regions displayed hyperexcitability, and the cingulate cortex showed hypoexcitability, which suggests that they are main candidate mediators of dysfunctional brain activation in pathologic anxiety.
There has been longstanding interest in the capacity of the immune system to access immunomodulatory glucocorticoid responses without invoking upstream neuroendocrine secretagogues, including CRH and ACTH. Here, we investigate the role of CRH and ACTH in adrenal glucocorticoid responses to murine cytomegalovirus (MCMV). Mice infected with MCMV exhibit IL-6-dependent glucocorticoid responses that peak at 36 h post infection and protect against cytokine (TNFalpha)-mediated lethality. Acute administration of a CRH-antibody (Ab) completely eliminated ACTH responses to both low- and high-dose MCMV. However, corticosterone responses in CRH-Ab-treated animals remained apparent in mice infected with low-dose MCMV and were robust in mice infected with high-dose MCMV. CRH-knockout (KO) mice exhibited robust corticosterone responses to both MCMV doses, despite reduced baseline and MCMV-induced ACTH. Interestingly, robust corticosterone responses in CRH-Ab-treated and CRH-KO mice were associated with exaggerated IL-6 levels, and IL-6 and corticosterone concentrations in infected CRH-Ab-treated animals were significantly correlated. Neutralization of IL-6 responses in infected CRH-KO mice reduced corticosterone responses by approximately 70%. Finally, MCMV-infected mice deprived of ACTH by hypophysectomy failed to elicit glucocorticoid responses, despite elevated plasma IL-6 concentrations. Taken together, these results suggest that a greater than normal induction of IL-6 compensates for the absence of a normal CRH-dependent ACTH surge during viral infection. This enhanced IL-6 response, in turn, may mediate a direct immune-adrenal pathway that can become a predominant driving force for glucocorticoid induction in the absence of CRH. However, the presence of ACTH appears to serve as a necessary permissive factor, enabling direct cytokine actions on the adrenal gland.