Regulation of gene expression by nitric oxide

Pfeilschifter, Josef; Eberhardt, W.; Beck, Karl‐Friedrich

doi:10.1007/s004240100586

Cited by 123 publications

(89 citation statements)

References 47 publications

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“…15,28,29 To identify NO-regulated genes that may be functionally important in the context of cardiac hypertrophy and failure, we analyzed the expression profile of 1176 genes in cardiac myocytes stimulated with the prohypertrophic polypeptide ET-1 in the presence or absence of the NO donor SNAP. Several genes were identified that were differentially regulated by NO ( Table).…”

Section: Discussionmentioning

confidence: 99%

“…2,11 Studies in NOS2-deficient and NOS2-overexpressing mice indicate that upregulation of NOS2 is detrimental and may increase mortality in heart failure. [12][13][14] The effects of NO in various cell types and tissues are mediated, in part, via changes in gene expression, 15 raising the possibility that transcriptional effects of NO may play a role in cardiac hypertrophy and failure as well. Little is known, however,…”

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confidence: 99%

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Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide

et al. 2003

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Background-In chronic heart failure, myocardial expression of the inducible isoform of nitric oxide (NO) synthase (NOS2) is enhanced, leading to a sustained production of NO. We postulated that NO modulates expression of genes in cardiac myocytes that may be functionally important in the context of cardiac hypertrophy and failure. Methods and Results-As revealed by cDNA expression array analyses, the NO donor SNAP, which has been shown previously to inhibit agonist-induced cardiac myocyte hypertrophy, downregulates expression of the cytoskeletonassociated muscle LIM protein (MLP) in endothelin-1 (ET-1)-stimulated neonatal rat cardiac myocytes. Northern blotting and immunoblotting experiments confirmed this finding and established that SNAP negatively controls MLP mRNA (Ϫ49%, PϽ0.01) and protein (Ϫ52%, PϽ0.01) abundance in ET-1-treated cardiomyocytes via cGMPdependent protein kinase and superoxide/peroxynitrite-dependent signaling pathways. Treatment of cardiac myocytes with IL-1␤ and IFN-␥ downregulated MLP expression levels via induction of NOS2. Moreover, expression levels of NOS2 and MLP were inversely correlated in the failing human heart, indicating that NOS2 may regulate MLP abundance in vitro and in vivo. Antisense oligonucleotides were used to explore the functional consequences of reduced MLP expression levels in cardiac myocytes. Like SNAP, antisense downregulation of MLP protein expression (Ϫ52%, PϽ0.01) blunted the increases in protein synthesis, cell size, and sarcomere organization in response to ET-1 stimulation. Conversely, overexpression of MLP augmented cell size and sarcomere organization in cardiac myocytes. Conclusions-NO negatively controls MLP expression in cardiac myocytes. Because MLP is necessary and sufficient for hypertrophy and sarcomere assembly, MLP downregulation may restrain hypertrophic growth in pathophysiological situations with increased cardiac NO production.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide

et al. 2003

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“…It has previously been suggested that NO produced by iNOS possess an influence on eNOS and nNOS expression at a transcriptional regulation level, as shown for a great number of genes including those for iNOS itself (see Pfeilschifter et al 2001). Furthermore, LPS-and cytokine-influenced variations in the regulation of eNOS mRNA expression have also been indicated (cf.…”

Section: Alterations In Nnos By MD Cells As Part Of Compensatory Intementioning

confidence: 91%

Expression of nitric oxide synthase isoforms in the mouse kidney: cellular localization and influence by lipopolysaccharide and Toll-like receptor 4

et al. 2006

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We determined the cellular mRNA expression of all intrarenal nitric oxide (NO)-producing NO synthase (NOS) isoforms, endothelial NOS (eNOS) and neuronal NOS (nNOS) and inducible NOS (iNOS) in kidneys from wild type mice (WT) and immune deficient Toll-like receptor 4 (TLR4) mutant mice, during normal physiological conditions and during a shortterm (6-16 hours) endotoxic condition caused by systemically administered lipopolysaccaride (LPS). Investigations were performed by means of in situ hybridization and polymerase chain reaction amplification techniques. In WT, LPS altered the expression rate of all intrarenal NOS isoforms in a differentiated but NOS-isoform coupled expression pattern, with iNOS induction, and up-and down-regulation of the otherwise constitutively expressed NOS isoforms, e.g. eNOS and nNOS and an iNOS isotype. In TLR4 mutants, LPS caused none or a lowered iNOS induction, but altered the expression rate of the constitutive NOS isoforms. It is concluded that the intrarenal spatial relation of individual NOS-isoforms and their alteration in expression provide the basis for versatile NO-mediated renal actions that may include local interactions between NOS isoforms and their individual NO-target sites, and that the NOSisoform dependent events are regulated by TLR4 during endotoxic processes. These regulatory mechanisms are likely to participate in different pathophysiological conditions affecting NO-mediated renal functions.

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“…Moreover, NO may also inhibit the expression of integrins, such as CD11a/CD18, in neutrophils (Banick et al 1997, Grisham et al 1998). Since NOS2 is involved in peroxynitrite-dependent tyrosine nitration (Sato et al 2000, Yeh et al 2007, it also regulates chemokine production and affects the inflammatory response mediated by IP-10, MCP-1, MIP-1a and MIP-2, and IL-8 (Mach et al 1999, Pfeilschifter et al 2001.…”

Section: No and The Immune Responsementioning

confidence: 99%