Pitavastatin induces PON1 expression through p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells

Arii, Kaoru; Suehiro, Tadashi; Ota, Kikuko; Ikeda, Yukio; Kumon, Yoshitaka; Osaki, Fumiaki; Inoue, Mari; Inada, Syojiro; Ogami, Naoko; Takata, Hiroshi; Hashimoto, Kozo; Terada, Yoshio

doi:10.1016/j.atherosclerosis.2008.05.013

Cited by 39 publications

(20 citation statements)

References 27 publications

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“…We reported that depletion of farnesyl pyrophosphate by pitavastatin was associated with pitavastatin-increased PON1 promoter activity in HepG2 cell [13]; moreover, it was recently reported that pitavastatin also induced PON1 expression through activation of the p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells [33]. To our best knowledge, it was only one report to refer the association with statins-influenced PKC activity and isoprenoids, which fluvastatin-decreased PKC activity was reversed by isoprenoids [30].…”

Section: Discussionmentioning

confidence: 88%

Role of protein kinase C in pitavastatin-induced human paraoxonase I expression in Huh7 cells

Arii¹,

Suehiro²,

Ikeda³

et al. 2010

Metabolism

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Section: Discussionmentioning

confidence: 88%

Role of protein kinase C in pitavastatin-induced human paraoxonase I expression in Huh7 cells

Arii¹,

Suehiro²,

Ikeda³

et al. 2010

Metabolism

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“…The consistency among the cellular studies and clinical application affirms the effects of simvastatin treatment, which has the potential to influence antiatherogenic mechanisms at the HDL level, thus providing evidence for one molecular mechanism by which PON expression could be regulated (83). In Huh7 cells, Arii et al found that pitavastatin treatment activates PON1 gene expression and increases PON1 protein expression by increasing the phosphorylation of p44/42 MAP kinases, probably by activating SREBP-2 and Sp1 and increasing their binding to PON1 DNA (18). Pitavastatin can also increase Sp1 binding to PON1 DNA by activating PKC, especially the PKCzeta isoform (17).…”

Section: Pharmacological Modulators Of Ponsmentioning

confidence: 99%

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

She

Chen

Yan

et al. 2012

Antioxidants & Redox Signaling

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The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar b propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence. Clinical observations focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Many other conditions, such as diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The abundance and/or activity of PONs can be regulated by lipoproteins and their metabolites, biological macromolecules, pharmacological treatments, dietary factors, and lifestyle. In conclusion, both previous results and ongoing studies provide evidence, making the PON cluster a prospective target for the treatment of atherosclerosis. Antioxid. Redox Signal. 16, 597-632.

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“…Pitavastatin was shown to increase the promoter activity and protein expression of PON1 in vitro. As for the mechanism, pitavastatin was revealed to promote PON1 expression via p44/42 MAP kinase-mediated phosphorylation of SREBP-2 and binding of Sp1 to PON1 DNA 123,124) . The increased PON1 activity was clinically confirmed with the administration of fluvastatin, simvastatin, atorvastatin and rosuvastatin [125][126][127][128] .…”

Section: ) Anti-oxidative Actionmentioning

confidence: 99%

Molecular Mechanisms of HDL-Cholesterol Elevation by Statins and Its Effects on HDL Functions

Yamashita

Tsubakio-Yamamoto

Ohama

et al. 2010

JAT

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Pitavastatin induces PON1 expression through p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells

Abstract: It has been shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have pleiotropic effects and that human serum paraoxonase (PON1) inhibits the oxidative modification of low-density lipoprotein. We investigated the

Cited by 39 publications

References 27 publications

Role of protein kinase C in pitavastatin-induced human paraoxonase I expression in Huh7 cells

Role of protein kinase C in pitavastatin-induced human paraoxonase I expression in Huh7 cells

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

Molecular Mechanisms of HDL-Cholesterol Elevation by Statins and Its Effects on HDL Functions

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