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Reciprocal Regulation (reciprocal + regulation)
Selected AbstractsReciprocal regulation of transcription factors and PLC isozyme gene expression in adult cardiomyocytesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Tushi Singal Abstract By employing a pharmacological approach, we have shown that phospholipase C (PLC) activity is involved in the regulation of gene expression of transcription factors such as c-Fos and c-Jun in cardiomyocytes in response to norepinephrine (NE). However, there is no information available regarding the identity of specific PLC isozymes involved in the regulation of c-Fos and c-Jun or on the involvement of these transcription factors in PLC isozyme gene expression in adult cardiomyocytes. In this study, transfection of cardiomyocytes with PLC isozyme specific siRNA was found to prevent the NE-mediated increases in the corresponding PLC isozyme gene expression, protein content and activity. Unlike PLC ,1 gene, silencing of PLC ,1, ,3 and ,1 genes with si RNA prevented the increases in c-Fos and c-Jun gene expression in response to NE. On the other hand, transfection with c-Jun si RNA suppressed the NE-induced increase in c-Jun as well as PLC ,1, ,3 and ,1 gene expression, but had no effect on PLC ,1 gene expression. Although transfection of cardiomyocytes with c-Fos si RNA prevented NE-induced expression of c-Fos, PLC ,1 and PLC ,3 genes, it did not affect the increases in PLC ,1 and PLC ,1 gene expression. Silencing of either c-Fos or c-Jun also depressed the NE-mediated increases in PLC ,1, ,3 and ,1 protein content and activity in an isozyme specific manner. Furthermore, silencing of all PLC isozymes as well as of c-Fos and c-Jun resulted in prevention of the NE-mediated increase in atrial natriuretic factor gene expression. These findings, by employing gene silencing techniques, demonstrate that there occurs a reciprocal regulation of transcription factors and specific PLC isozyme gene expression in cardiomyocytes. [source] Reciprocal regulation of the mouse protamine genes by the orphan nuclear receptor germ cell nuclear factor and CREM,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2004Geoffrey C. Hummelke Abstract Germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily, which is expressed in the adult predominantly in the male and female germ cells. In the male, GCNF is expressed in spermatogenic cells. GCNF binds as a homodimer to direct repeat response elements of the consensus half-site sequence, AGGTCA, with 0 bp spacing (DR0). Using this information, a search of genomic databases was performed to identify candidate GCNF responsive, spermatogenic-specific, genes that contain DR0 sequences. The mouse protamine genes are the strongest candidates identified to date, as they are post-meiotically expressed in round spermatids and contain DR0 elements in their proximal promoters. Previous work has shown that both recombinant and endogenous GCNF bind to DR0 elements in the mouse protamine 1 and 2 (Prm 1 and Prm 2) promoters with high affinity and specificity. The present work shows that in transient transfection assays in GC-1 and JEG-3 cells, co-transfection of a GCNF-VP16 expression plasmid with reporter plasmids containing either the wild type Prm 1 or Prm 2 promoter established that GCNF-VP16 is able to regulate transcription from both promoters in a DR0-dependent manner. Wild type GCNF, in contrast, acts as a repressor of basal transcription on both the Prm 1 and Prm 2 promoters in a DR0-dependent manner. Furthermore, CREM, activation of these promoters is also repressed by wild-type GCNF, indicating that GCNF also acts as a repressor of activated transcription. GCNF therefore defines a novel nuclear receptor-signaling pathway that may regulate a subset of genes involved in the terminal differentiation process of spermatogenesis, exemplified by the protamines. Mol. Reprod. Dev. 68: 394,407, 2004. © 2004 Wiley-Liss, Inc. [source] Reciprocal regulation of human soluble and particulate guanylate cyclases in vivoBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006M Madhani Background & purpose: We demonstrated previously that reciprocal regulation of soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we investigated whether such an interaction contributes to vascular homeostasis in mice and humans in vivo. Experimental approach: Mean arterial blood pressure (MABP) changes in anaesthetized mice were monitored in response to i.v. administration of cGMP- and cAMP-dependent vasodilators in wild-type (WT), endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25, 50, 100, 200 pmol min -1) in the absence and presence of the NOS inhibitor NG -methyl-L-arginine (L-NMA; 4 ,mol min -1) and the control constrictor noradrenaline (240 pmol min -1) was assessed in healthy volunteers. Key results: Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP) produced dose-dependent reductions in MABP in WT animals that were significantly enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent reduction in MABP that was significantly greater than that in WT mice. Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT, eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance vasculature that was significantly greater in individuals lacking endothelium-derived NO (i.e. L-NMA treated). Conclusions & implications: These data demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These findings have implications for understanding the link between natriuretic peptide activity and cardiovascular risk. British Journal of Pharmacology (2006) 149, 797,801. doi:10.1038/sj.bjp.0706920 [source] Expression of Gpr177, a Wnt trafficking regulator, in mouse embryogenesisDEVELOPMENTAL DYNAMICS, Issue 7 2010Hsiao-Man Ivy Yu Abstract Wls/Evi/Srt encoding a multipass transmembrane protein has been identified as a regulator for proper sorting and secretion of Wnt in flies. We have previously demonstrated that Gpr177 is the mouse ortholog required for axis determination. Gpr177 is a transcriptional target of Wnt that is activated to assist its subcellular distribution in a feedback regulatory loop. We, therefore, proposed that reciprocal regulation of Wnt and Gpr177 is essential for the Wnt-dependent developmental and pathogenic processes. Here, we examine the expression pattern of Gpr177 in mouse development. Gpr177 is expressed in a variety of tissues and cell types during organogenesis. Furthermore, Gpr177 is a glycoprotein primarily accumulating in the Golgi apparatus in signal-producing cells. The glycosylation of Gpr177 is necessary for proper transportation in the secretory pathway. Our findings suggest that the Gpr177-mediated regulation of Wnt is crucial for organogenesis in health and disease. Developmental Dynamics 239:2102,2109, 2010. © 2010 Wiley-Liss, Inc. [source] S -adenosylmethionine regulates dual-specificity mitogen-activated protein kinase phosphatase expression in mouse and human hepatocytes,HEPATOLOGY, Issue 6 2010Maria Lauda Tomasi Increased mitogen-activated protein kinase (MAPK) activity correlates with a more malignant hepatocellular carcinoma (HCC) phenotype. There is a reciprocal regulation between p44/42 MAPK (extracellular signal-regulated kinase [ERK]1/2) and the dual-specificity MAPK phosphatase MKP-1/DUSP1. ERK phosphorylates DUSP1, facilitating its proteasomal degradation, whereas DUSP1 inhibits ERK activity. Methionine adenosyltransferase 1a (Mat1a) knockout (KO) mice express hepatic S -adenosylmethionine (SAM) deficiency and increased ERK activity and develop HCC. The aim of this study was to examine whether DUSP1 expression is regulated by SAM and if so, elucidate the molecular mechanisms. Studies were conducted using Mat1a KO mice livers, cultured mouse and human hepatocytes, and 20S and 26S proteasomes. DUSP1 messenger RNA (mRNA) and protein levels were reduced markedly in livers of Mat1a KO mice and in cultured mouse and human hepatocytes with protein falling to lower levels than mRNA. SAM treatment protected against the fall in DUSP1 mRNA and protein levels in mouse and human hepatocytes. SAM increased DUSP1 transcription, p53 binding to DUSP1 promoter, and stability of its mRNA and protein. Proteasomal chymotrypsin-like and caspase-like activities were increased in Mat1a KO livers and cultured hepatocytes, which was blocked by SAM treatment. SAM inhibited chymotrypsin-like and caspase-like activities by 40% and 70%, respectively, in 20S proteasomes and caused rapid degradation of some of the 26S proteasomal subunits, which was blocked by the proteasome inhibitor MG132. SAM treatment in Mat1a KO mice for 7 days raised SAM, DUSP1, mRNA and protein levels and lowered proteosomal and ERK activities. Conclusion: DUSP1 mRNA and protein levels are lower in Mat1a KO livers and fall rapidly in cultured hepatocytes. SAM treatment increases DUSP1 expression through multiple mechanisms, and this may suppress ERK activity and malignant degeneration. HEPATOLOGY 2010 [source] Reciprocal regulation of transcription factors and PLC isozyme gene expression in adult cardiomyocytesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Tushi Singal Abstract By employing a pharmacological approach, we have shown that phospholipase C (PLC) activity is involved in the regulation of gene expression of transcription factors such as c-Fos and c-Jun in cardiomyocytes in response to norepinephrine (NE). However, there is no information available regarding the identity of specific PLC isozymes involved in the regulation of c-Fos and c-Jun or on the involvement of these transcription factors in PLC isozyme gene expression in adult cardiomyocytes. In this study, transfection of cardiomyocytes with PLC isozyme specific siRNA was found to prevent the NE-mediated increases in the corresponding PLC isozyme gene expression, protein content and activity. Unlike PLC ,1 gene, silencing of PLC ,1, ,3 and ,1 genes with si RNA prevented the increases in c-Fos and c-Jun gene expression in response to NE. On the other hand, transfection with c-Jun si RNA suppressed the NE-induced increase in c-Jun as well as PLC ,1, ,3 and ,1 gene expression, but had no effect on PLC ,1 gene expression. Although transfection of cardiomyocytes with c-Fos si RNA prevented NE-induced expression of c-Fos, PLC ,1 and PLC ,3 genes, it did not affect the increases in PLC ,1 and PLC ,1 gene expression. Silencing of either c-Fos or c-Jun also depressed the NE-mediated increases in PLC ,1, ,3 and ,1 protein content and activity in an isozyme specific manner. Furthermore, silencing of all PLC isozymes as well as of c-Fos and c-Jun resulted in prevention of the NE-mediated increase in atrial natriuretic factor gene expression. These findings, by employing gene silencing techniques, demonstrate that there occurs a reciprocal regulation of transcription factors and specific PLC isozyme gene expression in cardiomyocytes. [source] Temperature-induced regulation of RpoS by a small RNA in Borrelia burgdorferiMOLECULAR MICROBIOLOGY, Issue 4 2007Meghan C. Lybecker Summary The alternative sigma factor RpoS (,38 or ,S) plays a central role in the reciprocal regulation of the virulence-associated major outer surface proteins OspC and OspA in Borrelia burgdorferi, the Lyme disease spirochete. Temperature is one of the key environmental signals controlling RpoS, but the molecular mechanism by which the signal is transduced remains unknown. Herein, we identify and describe a small non-coding RNA, DsrABb, that regulates the temperature-induced increase in RpoS. A novel 5, end of the rpoS mRNA was identified and DsrABb has the potential to extensively base-pair with the upstream region of this rpoS transcript. We demonstrate that B. burgdorferi strains lacking DsrABb do not upregulate RpoS and OspC in response to an increase in temperature, but do regulate RpoS and OspC in response to changes in pH and cell density. Analyses of the rpoS and ospC steady-state mRNA levels in the dsrABb mutant indicate that DsrABb regulates RpoS post-transcriptionally. The 5, and 3, ends of DsrABb were mapped, demonstrating that at least four species exist with sizes ranging from 213 to 352 nucleotides. We hypothesize that DsrABb binds to the upstream region of the rpoS mRNA and stimulates translation by releasing the Shine-Dalgarno sequence and start site from a stable secondary structure. Therefore, we postulate that DsrABb is a molecular thermometer regulating RpoS in Borrelia burgdorferi. [source] Reciprocal regulation of human soluble and particulate guanylate cyclases in vivoBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006M Madhani Background & purpose: We demonstrated previously that reciprocal regulation of soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we investigated whether such an interaction contributes to vascular homeostasis in mice and humans in vivo. Experimental approach: Mean arterial blood pressure (MABP) changes in anaesthetized mice were monitored in response to i.v. administration of cGMP- and cAMP-dependent vasodilators in wild-type (WT), endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25, 50, 100, 200 pmol min -1) in the absence and presence of the NOS inhibitor NG -methyl-L-arginine (L-NMA; 4 ,mol min -1) and the control constrictor noradrenaline (240 pmol min -1) was assessed in healthy volunteers. Key results: Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP) produced dose-dependent reductions in MABP in WT animals that were significantly enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent reduction in MABP that was significantly greater than that in WT mice. Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT, eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance vasculature that was significantly greater in individuals lacking endothelium-derived NO (i.e. L-NMA treated). Conclusions & implications: These data demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These findings have implications for understanding the link between natriuretic peptide activity and cardiovascular risk. British Journal of Pharmacology (2006) 149, 797,801. doi:10.1038/sj.bjp.0706920 [source] Growth Hormone Secretagogue Actions On The Pituitary Gland: Multiple Receptors For Multiple Ligands?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2000Chen Chen SUMMARY 1. Growth hormone (GH) secretion is thought to occur under the reciprocal regulation of two hypothalamic hormones, namely GH-releasing hormone (GHRH) and somatostatin (SRIF), through their engagement with specific cell-surface receptors on the anterior pituitary somatotropes. 2. In addition to GHRH and SRIF, synthetic GH-releasing peptides (GHRP) or GH secretagogue(s) (GHS) regulate GH release through the activation of a novel receptor, the GHS receptor (GHS-R). 3. The cloning of the GHS-R from human, swine and rat identifies a novel G-protein-coupled receptor involved in the control of GH secretion and supports the existence of an undiscovered hormone that may activate this receptor. 4. Varieties of intracellular signalling systems are suggested to mediate the action of GHS, which include changes in intracellular free Ca2+ ([Ca2+]i), cAMP, protein kinases A and C, phospholipase C etc. 5. With regard to the use of signalling systems by GHS, especially a new form of GHRP or GHRP-2, a clear species difference has been demonstrated, supporting the possibility of more than one type of GHS-R. [source] | |||||||||||||