Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes.

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Abstract Text:

Kozo Habara,Yoshinori Hamada,Masanori Yamada,Katsuji Tokuhara,Hironori Tanaka,Masaki Kaibori,Yasuo Kamiyama,Mikio Nishizawa,Seiji Ito,Tadayoshi Okumura,Kozo Habara,Yoshinori Hamada,Masanori Yamada,Katsuji Tokuhara,Hironori Tanaka,Masaki Kaibori,Yasuo Kamiyama,Mikio Nishizawa,Seiji Ito,Tadayoshi Okumura,

Studies have indicated that protective effects of statins (HMG-CoA reductase inhibitor) are associated with the regulation of endothelial nitric oxide synthase (eNOS) or inducible NOS (iNOS) in heart and liver diseases. Statins have been reported to enhance hepatic NO production and decrease the vascular tone in patients with cirrhosis. However, it is unclear which NOS contributes to the increased NO production. We hypothesized that statins are involved in the up-regulation of iNOS in inflammatory liver, resulting in decreased hepatic resistance. Primary cultured rat hepatocytes were treated with pro-inflammatory cytokine interleukin (IL)-1beta in the presence or absence of pitavastatin. Pretreatment of cells with pitavastatin resulted in up-regulation of iNOS induction by IL-1beta, followed by increased NO production. Pitavastatin had no effects on the degradation of IkappaB or activation of NF-kappaB. However, pitavastatin super-induced the up-regulation of type I IL-1 receptor (IL-1RI), which is essential for iNOS induction in addition to the IkappaB/NF-kappaB pathway. Mevalonate and geranylgeranylpyrophosphate blocked the stimulatory effects of pitavastatin on iNOS and IL-1RI induction. Transfection experiments revealed that pitavastatin increased the stability of iNOS mRNA rather than its promoter transactivation. In support of this observation, pitavastatin increased the antisense-transcript corresponding to the 3'-UTR of iNOS mRNA, which stabilizes iNOS mRNA by interacting with the 3'-UTR- and RNA-binding proteins. These findings demonstrate that pitavastatin up-regulates iNOS by the stabilization of its mRNA, presumably through the super-induction of IL-1RI and antisense-transcript. This implies that statins may contribute to a novel potentiated treatment in liver injuries including cirrhosis.

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Publishing Authors By Initials

K Habara,Y Hamada,M Yamada,K Tokuhara,H Tanaka,M Kaibori,Y Kamiyama,M Nishizawa,S Ito,T Okumura,K Habara,Y Hamada,M Yamada,K Tokuhara,H Tanaka,M Kaibori,Y Kamiyama,M Nishizawa,S Ito,T Okumura,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nitric oxide : biology and chemistry / official jo

VOLUME: 18

Page Numbers: 19-27

Journal Abbreviation: Nitric Oxide

ISSN: 1089-8603

DAY: 7

MONTH: 09

YEAR: 2007

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9709307

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes.

AFFILIATION: Department of Surgery, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Nitric Oxide

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes Related Publications

• Aldosterone causes vasoconstriction in coronary arterioles of rats via angiotensin II type-1 receptor: influence of hypertension.
• Automated Discrimination of Tissue Boundaries using Ultrasound Images of "Ubiquitous Echo".
• Automatic anatomical labeling method of cerebral arteries in MR-angiography data set.
• Beneficial effect of neutrophil elastase inhibitor on anti-Thy1.1 nephritis in rats.
• Characterization of alternatively spliced isoforms of the type I interleukin-1 receptor on iNOS induction in rat hepatocytes.
• Chemosensitivity assessed by collagen gel droplet embedded culture drug sensitivity test, and MDR1, MRP1, and MRP2 mRNA expression in human colorectal adenocarcinomas.
• Determination of the absolute configuration of urothion.
• Effect of active hexose correlated compound on the production of nitric oxide in hepatocytes.
• Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes.
• Effects of bilateral and unilateral eyestalk ablation on vitellogenin synthesis in immature female kuruma prawns, Marsupenaeus japonicus.
• Effects of lipopolysaccharide on gene expression of antimicrobial peptides (penaeidins and crustin), serine proteinase and prophenoloxidase in haemocytes of the Pacific white shrimp, Litopenaeus vannamei.
• Expression of humanized Fab fragments that recognize the IgE-binding domain of human Fc(epsilon)RIalpha in COS and CHO cells.
• Glycaemic control and serum intact parathyroid hormone levels in diabetic patients on haemodialysis therapy.
• Impact of the high-molecular-weight form of adiponectin on endothelial function in healthy young men.
• Improvement in image quality of noncontrast head images in multidetector-row CT by volume helical scanning with a three-dimensional denoising filter.
• Interaction of alpha1-syntrophin with multiple isoforms of heterotrimeric G protein alpha subunits.
• Lipopolysaccharide induces adipose differentiation-related protein expression and lipid accumulation in the liver through inhibition of fatty acid oxidation in mice.
• MSPL/TMPRSS13.
• Microanalysis of action patterns of amylolytic enzymes: identification of a glucose-forming amylase in Japanese radish root.
• Na(+)/H(+) exchanger inhibitor, FR183998, has protective effect in lethal acute liver failure and prevents iNOS induction in rats.
• Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction.
• Orotate as a beta-alanine donor for anserine and carnosine biosynthesis, and effects of actinomycin D and azauracil on their pathway.
• Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes.
• Rebamipide, anti-gastric ulcer drug, up-regulates the induction of iNOS in proinflammatory cytokine-stimulated hepatocytes.
• The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels.
• Transition-metal-mediated cascade reactions: C,C-dicyclopropylmethylamines by way of double C,C-sigma-bond insertion into bicyclobutanes.
• [Arrhythmias in dialysis patients]
• [Gastric lavage]
• [Metabolic syndrome]
• [The role of a memory clinic in regional supporting system for mild dementia patients and caregivers]