			Home About us Contact

Tissue-specific Regulation (tissue-specific + regulation)

Distribution by Scientific Domains

Life Sciences	57%
Medical Sciences	28%

Selected Abstracts

Tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-, knock-out mice

EXPERIMENTAL PHYSIOLOGY, Issue 5 2008
K. Bridget Brosnihan
Angiotensin-converting enzyme (ACE) and ACE2 and the AT1 and AT2 receptors are pivotal points of regulation in the renin,angiotensin system. ACE and ACE2 are key enzymes in the formation and degradation of angiotensin II (Ang II) and angiotensin-(1,7)(Ang-(1,7)). Ang II acts at either the AT1 or the AT2 receptor to mediate opposing actions of vasoconstriction or vasodilatation respectively. While it is known that oestrogen acts to downregulate ACE and the AT1 receptor, its regulation of ACE2 and the AT2 receptor and the involvement of a specific oestrogen receptor subtype are unknown. To investigate the role of oestrogen receptor-, (ER,) in the regulation by oestrogen of ACE/ACE2 and AT1/AT2 mRNAs in lung and kidney, ovariectomized female mice lacking apolipoprotein E (ee) with the ER, (AAee) or without the ER, (,,ee) were treated with 17,-oestradiol (6 ,g day,1) or placebo for 3 months. ACE, ACE2, AT1 receptor and AT2 receptor mRNAs were measured using reverse transcriptase, real-time polymerase chain reaction. In the kidney, 17,-oestradiol showed 1.7-fold downregulation of ACE mRNA in AAee mice, with 2.1-fold upregulation of ACE mRNA in ,,ee mice. 17,-Oestradiol showed 1.5- and 1.8-fold downregulation of ACE2 and AT1 receptor mRNA in AAee mice; this regulation was lost in ,,ee mice. 17,-Oestradiol showed marked (81-fold) upregulation of the AT2 receptor mRNA in AAee mice. In the lung, 17,-oestradiol treatment had no effect on AT1 receptor mRNA in AAee mice, but resulted in a 1.5-fold decreased regulation of AT1 mRNA in ,,ee mice. There was no significant interaction of oestrogen with ER, in the lung for ACE, ACE2 and AT2 receptor genes. These studies reveal tissue-specific regulation by 17,-oestradiol of ACE/ACE2 and AT1/AT2 receptor genes, with the ER, receptor being primarily responsible for the regulation of kidney ACE2, AT1 receptor and AT2 receptor genes. [source]

The death of cardiotonic steroid-treated cells: evidence of Na+i,K+i -independent H+i -sensitive signalling

ACTA PHYSIOLOGICA, Issue 1-2 2006
S. N. Orlov
Abstract Na/K-ATPase is the only known target of cardiotonic steroids (CTS) identified in plants, amphibians and later on in several mammalian species, including human. We focus our review on recent data implicating CTS in the tissue-specific regulation of cell survival and death. In vascular smooth muscle cells, CTS inhibited cell death triggered by apoptotic stimuli via a novel Na+i -mediated, Ca2+i -independent mechanism of expression of antiapoptotic genes, including mortalin. In contrast, exposure to CTS in vascular endothelial and renal epithelial cells led to cell death, showing combined markers of apoptosis and necrosis. This mode of cell death, termed oncosis, is caused by CTS interaction with Na/K-ATPase but is independent of the inhibition of Na/K-ATPase-mediated ion fluxes and inversion of the [Na+]i/[K+]i ratio. The intermediates of intracellular signalling involved in Na+i, K+i -independent oncosis of CTS-treated cells remain unknown. Recently, we found that this mode of cell death can be protected by modest intracellular acidification via the expression of H+i -sensitive genes. The molecular origin of intracellular Na+ and H+ sensor involvement in the development of apoptosis and oncosis is currently under investigation. [source]

Tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-, knock-out mice

Chromatin structure of the bovine Cyp19 promoter 1.1

FEBS JOURNAL, Issue 5 2001
DNA hypomethylation correlate with placental expression, DNaseI hypersensitive sites
Expression of the Cyp19 gene, encoding aromatase cytochrome P450, is driven by several tissue-specific promoters. The underlying mechanisms of this complex regulation have not yet been elucidated in detail. In the present report we investigate a possible link between chromatin structure and tissue-specific regulation of the bovine Cyp19 gene. We analysed the DNA methylation status and mapped DNaseI hypersensitive sites in the region encompassing the Cyp19 promoter 1.1 (P1.1) which controls Cyp19 expression in the bovine placenta. We show that P1.1 is hypomethylated in placental cotyledons (foetal layer) whereas it is methylated in placental caruncles (maternal layer), testis and corpus luteum. Furthermore, two placenta-specific DNaseI hypersensitive sites, HS1 and HS2, were observed within P1.1. Both DNA hypomethylation and the presence of DNaseI hypersensitive sites correlate with transcriptional activity of P1.1. Sequence analysis of hypersensitive sites revealed potential cis -regulatory elements, an E-box in HS1 and a trophoblast-specific element-like sequence in HS2. It could be demonstrated by electrophoretic mobility shift assays that both sequence motifs are specific targets for placenta-derived nuclear factors. In conclusion, observed tissue-specific differences of the chromatin structure which correlate with tissue-specific promoter activity suggest that chromatin might be an important regulator of aromatase expression in cattle. [source]

Regulation and Expression of Progesterone Receptor mRNA Isoforms A and B in the Male and Female Rat Hypothalamus and Pituitary Following Oestrogen Treatment

JOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2002
R. E. M. Scott
Abstract Progesterone receptors play a central role in neuroendocrine and behavioural regulation. To gain insight into the sex- and tissue-specific regulation of progesterone receptors, protein binding on a progesterone receptor-oestrogen response element and mRNA levels for progesterone receptor (PR)-A and PR-B were compared between female and male rats following oestradiol benzoate replacement treatment in hypothalamic and pituitary tissue. Both male and female pituitary protein extracts demonstrated an increase in nuclear protein binding activity to a progesterone receptor-oestrogen response element following oestradiol benzoate treatment. However, there was a greater difference in total binding activity seen in the female pituitary extracts compared to male pituitary protein extracts. In both cases, reflecting the binding data, oestradiol benzoate pretreatment led to an increase in pituitary PR-B messenger RNA, although this increase was significantly larger in females than in males. Oestradiol benzoate treatment also led to a significant increase in specific binding of hypothalamic nuclear proteins to the progesterone receptor oestrogen response element from both females and male hypothalamic extracts. In addition, PR-B messenger RNA was induced by oestradiol benzoate treatment in the female rat hypothalamus, under circumstances where no PR-A could be detected. The male also demonstrated an increase in PR-B messenger RNA following oestradiol benzoate treatment, with undetectable levels of PR-A, although to a lesser degree than that seen in the female. The predominance of PR-B over PR-A messenger RNA in rat hypothalamus and pituitary, and the quantitative differences between female and male rats, could both contribute to the greater responsiveness of female rats to progesterone with respect to control over luteinizing hormone release from the pituitary, and lordosis behaviour regulated by hypothalamic neurones. [source]

In situ assays demonstrate that interferon-gamma suppresses infection-stimulated hepatic fibrin deposition by promoting fibrinolysis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2006
I. K. MULLARKY
Summary.,Background:,Inflammatory cytokines potently impact hemostatic pathways during infection, but the tissue-specific regulation of coagulation and fibrinolysis complicates studies of the underlying mechanisms. Methods and Results:,Here, we describe assays that quantitatively measuring prothrombinase (PTase), protein C-ase (PCase) and plasminogen activator (PA) activities in situ, thereby facilitating studies of tissue-specific hemostasis. Using these assays, we investigate the mechanisms regulating hepatic fibrin deposition during murine toxoplasmosis and the means by which interferon-gamma (IFN- ,) suppresses infection-stimulated fibrin deposition. We demonstrate that Toxoplasma infection upregulates hepatic PTase, PCase, and PA activity. Wild type and gene-targeted IFN- , -deficient mice exhibit similar levels of infection-stimulated PTase activity. By contrast, IFN- , -deficiency is associated with increased PCase activity and reduced PA activity during infection. Parallel analyses of hepatic gene expression reveal that IFN- , -deficiency is associated with increased expression of thrombomodulin (TM), a key component of the PCase, increased expression of thrombin-activatable fibrinolysis inhibitor (TAFI), a PC substrate, and reduced expression of urokinase PA (u-PA). Conclusions:,These findings suggest that IFN- , suppresses infection-stimulated hepatic fibrin deposition by suppressing TM-mediated activation of TAFI, thereby destabilizing fibrin deposits, and concomitantly increasing hepatic u-PA activity, thereby promoting fibrinolysis. We anticipate that further application of these in situ assays will improve our understanding of tissue-specific hemostasis, its regulation by cytokines, and its dysregulation during coagulopathy. [source]

The role of DNA methylation, nucleosome occupancy and histone modifications in paramutation

THE PLANT JOURNAL, Issue 3 2010
Max Haring
Summary Paramutation is the transfer of epigenetic information between alleles that leads to a heritable change in expression of one of these alleles. Paramutation at the tissue-specifically expressed maize (Zea mays) b1 locus involves the low-expressing B, and high-expressing B-I allele. Combined in the same nucleus, B, heritably changes B-I into B,. A hepta-repeat located 100-kb upstream of the b1 coding region is required for paramutation and for high b1 expression. The role of epigenetic modifications in paramutation is currently not well understood. In this study, we show that the B, hepta-repeat is DNA-hypermethylated in all tissues analyzed. Importantly, combining B, and B-I in one nucleus results in de novo methylation of the B-I repeats early in plant development. These findings indicate a role for hepta-repeat DNA methylation in the establishment and maintenance of the silenced B, state. In contrast, nucleosome occupancy, H3 acetylation, and H3K9 and H3K27 methylation are mainly involved in tissue-specific regulation of the hepta-repeat. Nucleosome depletion and H3 acetylation are tissue-specifically regulated at the B-I hepta-repeat and associated with enhancement of b1 expression. H3K9 and H3K27 methylation are tissue-specifically localized at the B, hepta-repeat and reinforce the silenced B, chromatin state. The B, coding region is H3K27 dimethylated in all tissues analyzed, indicating a role in the maintenance of the silenced B, state. Taken together, these findings provide insight into the mechanisms underlying paramutation and tissue-specific regulation of b1 at the level of chromatin structure. [source]