Home About us Contact
|
Home About us Contact | ||
|
|
||
Regulatory Mechanisms Underlying (regulatory + mechanism_underlying)
Selected AbstractsCatalytic activity of Cdk9 is required for nuclear co-localization of the Cdk9/cyclin T1 (P-TEFb) complexJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2003Giuliana Napolitano Cdk9 and its binding partner cyclin T1 comprise the positive elongation factor b (P-TEFb). P-TEFb phosphorylates the RNA polymerase II carboxyl-terminal-domain (CTD) allowing efficient transcription elongation. Recent studies showed that Cdk9 is a predominant nuclear protein, and here we investigated the functional requirement for nuclear localization of Cdk9. We found that the catalytic inactive kinase mutant (Cdk9dn) fails to accumulate in the nucleus showing a diffuse sub-cellular localization. In addition to the catalityc activity, nuclear localization of Cdk9 protein requires the presence of the phospho-acceptor sites at the C-terminus tail. Finally, enforced expression of wild-type cyclinT1, which enhances nuclear localization of Cdk9wt, fails to direct the Cdk9 mutants to the nucleus. Collectively, these findings implicate that nuclear localization of Cdk9 requires auto-phosphorylation of the kinase, and highlight the presence of a regulatory mechanism underlying the nuclear localization of the P-TEFb complex. J. Cell. Physiol. 197: 1,7, 2003© 2003 Wiley-Liss, Inc. [source] GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004Mario Engelmann Abstract Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA -receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion. [source] Taurine selectively modulates the secretory activity of vasopressin neurons in conscious ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001Mario Engelmann Abstract Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states. [source] Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profilingTHE JOURNAL OF PATHOLOGY, Issue 1 2005Xiaojuan Sun Abstract Malignant mesothelioma is an aggressive tumour, characterized by a variable differentiation pattern and poor prognosis. At present, the clinical outcome in patients with malignant mesothelioma is mainly predicted by the morphological phenotype of the tumour. However, this conventional clinicopathological parameter is of limited value, partly because of the biological heterogeneity of this tumour and poor understanding of the regulatory mechanisms underlying the various patterns of growth. To elucidate the intrinsic molecular programmes that determine tumour differentiation, oligonucleotide arrays were used in an in vitro model of mesothelioma differentiation. The analysis of 2059 genes detected 102 genes that were significantly deregulated. Clustering of these genes into functional categories showed distinctive patterns for the two phenotypes, namely epithelioid and sarcomatoid. The molecular fingerprint of the sarcomatoid tumour component indicates overrepresentation of growth factor receptors and growth factor binding proteins, whereas epithelioid mesothelioma cells express other tumour-promoting factors involved in differentiation, metabolism, and regulation of apoptosis. These differences in the molecular phenotype may give a better basis for diagnosis and for designing novel therapies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | ||||||||||