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Independent Regulation (independent + regulation)
Selected AbstractsIndependent Regulation of Periarteriolar and Perivenular Nitric Oxide Mechanisms in the In Vivo Hamster Cheek Pouch MicrovasculatureMICROCIRCULATION, Issue 4 2009DAVID D. KIM ABSTRACT Objective: We tested the hypothesis that differential stimulation of nitric oxide (NO) production can be induced in pre- and postcapillary segments of the microcirculation in the hamster cheek pouch. Materials and Methods: We applied acetylcholine (ACh) or platelet-activating factor (PAF) topically and measured perivascular NO concentration ([NO]) with NO-sensitive microelectrodes in arterioles and venules of the hamster cheek pouch. We also measured NO in cultured coronary endothelial cells (CVEC) after ACh or PAF. Results: ACh increased periarteriolar [NO] significantly in a dose-dependent manner. ACh at 1 ,M increased [NO] from 438.1±43.4 nM at baseline to 647.9±66.3 nM, while 10 ,M of ACh increased [NO] from baseline to 1,035.0±59.2 nM (P<0.05). Neither 1 nor 10 ,M of ACh changed perivenular [NO] in the hamster cheek pouch. PAF, at 100 nM, increased perivenular [NO] from 326.6±50.8 to 622.8±41.5 nM. Importantly, 100 nM of PAF did not increase periarteriolar [NO]. PAF increased [NO] from 3.6±2.1 to 455.5±19.9 in CVEC, while ACh had no effect. Conclusions: We conclude that NO production can be stimulated in a differential manner in pre- and postcapillary segments in the hamster cheek pouch. ACh selectively stimulates the production of NO only in arterioles, while PAF stimulates the production of NO only in venules. [source] The regulation of muscle glycogen: the granule and its proteinsACTA PHYSIOLOGICA, Issue 4 2010T. E. Graham Abstract Despite decades of studying muscle glycogen in many metabolic situations, surprisingly little is known regarding its regulation. Glycogen is a dynamic and vital metabolic fuel that has very limited energetic capacity. Thus its regulation is highly complex and multifaceted. The stores in muscle are not homogeneous and there appear to be various metabolic pools. Each granule is capable of independent regulation and fundamental aspects of the regulation appear to be associated with a complex set of proteins (some are enzymes and others serve scaffolding roles) that associate both with the granule and with each other in a dynamic fashion. The regulation includes altered phosphorylation status and often translocation as well. The understanding of the roles and the regulation of glycogenin, protein phosphatase 1, glycogen targeting proteins, laforin and malin are in their infancy. These various processes appear to be the mechanisms that give the glycogen granule precise, yet dynamic regulation. [source] IRAK-4 kinase activity-dependent and -independent regulation of lipopolysaccharide-inducible genesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008Magdalena Koziczak-Holbro Abstract IRAK-4 kinase inactive (IRAK-4 KD) knock-in mice display defects in TLR- and IL-1 receptor signaling and are resistant to LPS-induced shock. In the present study we examined the LPS-induced response in IRAK-4 KD mice in more detail. We show that IRAK-4 kinase activity is required for certain aspects of TLR-mediated signaling but not for others. We found that IRAK-4 KD cells displayed reduced JNK and p38 signaling, while NF-,B was activated to a normal level but with delayed kinetics compared to wild-type cells. TLR4-mediated IRF3 activation was intact in these cells. Comprehensive analysis of expression of LPS-inducible genes by microarray demonstrated that IRAK-4 KD cells were severely impaired in the expression of many pro-inflammatory genes, suggesting their dependence on IRAK-4 kinase activity. In contrast, the expression of a subset of LPS-induced genes of anti-viral response was not affected by IRAK-4 kinase deficiency. Additionally, we demonstrate that LPS-activated early expression and production of some cytokines, e.g., TNF-,, is partially induced in the absence of IRAK-4 kinase activity. This suggests that the partially unaffected TLR4-mediated signaling could still drive expression of these genes in early phases and that IRAK-4 kinase activity is important for a more sustained anti-bacterial response. See accompanying commentary http://dx.doi.org/10.1002/eji.200838161 [source] Vasoconstrictively Acting AT1R A1166C and NOS3 4/5 Polymorphisms in Recurrent Spontaneous Abortions (RSA),AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2004Tina Buchholz Problem:, Inadequate uteroplacental perfusion is one of the main reasons for recurrent spontaneous abortions (RSA). Coagulation, fibrinolysis, and vasoconstriction affect tissue perfusion. These systems are regulated by different gene products. Polymorphisms can modulate the expression levels of the respective genes and can thereby affect perfusion. Vasoconstriction is influenced by the expression of endothelial nitric oxide synthase (eNOS) and of the angiotensinogen II type 1 receptor (AT1R). Method:, The aim of our study was to investigate, whether two polymorphisms in the AT1R and NOS3 genes shown to result in maternal vasoconstriction are associated with an increased risk for RSA. Results:, Our data indicate that the vasoconstrictively acting genotypes AT1R C/C and NOS3 4/4 are of similar prevalence in RSA patients and in controls. Conclusion:, Results do not show any influence of the polymorphisms studied on early pregnancy development. This is in concordance with the concept of an independent regulation of placental perfusion. [source] TNF Receptors Differentially Signal and Are Differentially Expressed and Regulated in the Human HeartAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009R. S. Al-Lamki Tumor necrosis factor (TNF) utilizes two receptors, TNFR1 and 2, to initiate target cell responses. We assessed expression of TNF, TNFRs and downstream kinases in cardiac allografts, and compared TNF responses in heart organ cultures from wild-type (WTC57BL/6), TNFR1-knockout (KO), TNFR2KO, TNFR1/2KO mice. In nonrejecting human heart TNFR1 was strongly expressed coincidentally with inactive apoptosis signal-regulating kinase-1 (ASK1) in cardiomyocytes (CM) and vascular endothelial cells (VEC). TNFR2 was expressed only in VEC. Low levels of TNF localized to microvessels. Rejecting cardiac allografts showed increased TNF in microvessels, diminished TNFR1, activation of ASK1, upregulated TNFR2 co-expressed with activated endothelial/epithelial tyrosine kinase (Etk), increased apoptosis and cell cycle entry in CM. Neither TNFR was expressed significantly by cardiac fibroblasts. In WTC57BL/6 myocardium, TNF activated both ASK1 and Etk, and increased both apoptosis and cell cycle entry. TNF-treated TNFR1KO myocardium showed little ASK1 activation and apoptosis but increased Etk activation and cell cycle entry, while TNFR2KO myocardium showed little Etk activation and cell cycle entry but increased ASK1 activation and apoptosis. These observations demonstrate independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1-mediated cell death and TNFR2-mediated repair. [source] ,Klotho: A new kid on the bile acid biosynthesis block,HEPATOLOGY, Issue 1 2006Marco Arrese We have generated a line of mutant mouse that lacks ,Klotho, a protein that structurally resembles Klotho. The synthesis and excretion of bile acids were found to be dramatically elevated in these mutants, and the expression of 2 key bile acid synthase genes, cholesterol 7,-hydroxylase (Cyp7a1) and sterol 12,- hydroxylase (Cyp8b1), was strongly upregulated. Nuclear receptor pathways and the enterohepatic circulation, which regulates bile acid synthesis, seemed to be largely intact; however, bile acid,dependent induction of the small heterodimer partner (SHP) NR0B2, a common negative regulator of Cyp7a1 and Cyp8b1, was significantly attenuated. The expression of Cyp7a1 and Cyp8b1 is known to be repressed by dietary bile acids via both SHP-dependent and -independent regulations. Interestingly, the suppression of Cyp7a1 expression by dietary bile acids was impaired, whereas that of Cyp8b1 expression was not substantially altered in ,klotho,/, mice. Therefore, ,Klotho may stand as a novel contributor to Cyp7a1 -selective regulation. Additionally, ,Klotho-knockout mice exhibit resistance to gallstone formation, which suggests the potential future clinical relevance of the ,Klotho system. [source] | ||||||||||