Functional connections and pathways of coenzyme Q10‐inducible genes: An in‐silico study

Döring, Frank; Schmelzer, Constance; Lindner, Inka; Vock, Christina; Fukui, Kenji

doi:10.1080/15216540701545991

Cited by 60 publications

(24 citation statements)

References 46 publications

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“…Here we hypothesized that the reduced form of Coenzyme Q 10 (QH 2 , ubiquinol-10) affects LPS-inducible expression of the anti-inflammatory miR-146a. The hypothesis was based on functions of CoQ 10 as a potent antioxidant and putative modulator of inflammation via gene expression [8, 9]. In the present work, we tested our hypothesis using an in vitro and an in vivo model.…”

Section: Introductionmentioning

confidence: 89%

Effects of Ubiquinol-10 on MicroRNA-146a Expression In Vitro and In Vivo

Schmelzer

Kitano

Rimbach

et al. 2009

Mediators of Inflammation

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MicroRNAs (miRs) are involved in key biological processes via suppression of gene expression at posttranscriptional levels. According to their superior functions, subtle modulation of miR expression by certain compounds or nutrients is desirable under particular conditions. Bacterial lipopolysaccharide (LPS) induces a reactive oxygen species-/NF-κB-dependent pathway which increases the expression of the anti-inflammatory miR-146a. We hypothesized that this induction could be modulated by the antioxidant ubiquinol-10. Preincubation of human monocytic THP-1 cells with ubiquinol-10 reduced the LPS-induced expression level of miR-146a to 78.9 ± 13.22%. In liver samples of mice injected with LPS, supplementation with ubiquinol-10 leads to a reduction of LPS-induced miR-146a expression to 78.12 ± 21.25%. From these consistent in vitro and in vivo data, we conclude that ubiquinol-10 may fine-tune the inflammatory response via moderate reduction of miR-146a expression.

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Section: Introductionmentioning

confidence: 89%

Effects of Ubiquinol-10 on MicroRNA-146a Expression In Vitro and In Vivo

Schmelzer

Kitano

Rimbach

et al. 2009

Mediators of Inflammation

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“…For instance, UQ 10 influences the expression of hundreds of human genes involved in different cellular pathways. Among them, seventeen are functionally connected by signaling pathways of G-protein coupled receptor, JAK/STAT, integrin and β-arrestin (Schmelzer et al, 2007). These UQ 10 -inducible genes possess a common promoter framework with binding domains of transcription factor families EVII, HOXF, HOXC and CLOX (Schmelzer et al, 2007).…”

Section: Physiological Functions Of Pq and Uq In Plantsmentioning

confidence: 99%

“…Among them, seventeen are functionally connected by signaling pathways of G-protein coupled receptor, JAK/STAT, integrin and β-arrestin (Schmelzer et al, 2007). These UQ 10 -inducible genes possess a common promoter framework with binding domains of transcription factor families EVII, HOXF, HOXC and CLOX (Schmelzer et al, 2007). Moreover, UQ 10 –mediated gene-gene network are involved in inflammation, cell differentiation, and peroxisome proliferator-activated receptor signaling (Schmelzer et al, 2011).…”

Section: Physiological Functions Of Pq and Uq In Plantsmentioning

confidence: 99%

Plastoquinone and Ubiquinone in Plants: Biosynthesis, Physiological Function and Metabolic Engineering

Liu

2016

Front. Plant Sci.

124

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Plastoquinone (PQ) and ubiquinone (UQ) are two important prenylquinones, functioning as electron transporters in the electron transport chain of oxygenic photosynthesis and the aerobic respiratory chain, respectively, and play indispensable roles in plant growth and development through participating in the biosynthesis and metabolism of important chemical compounds, acting as antioxidants, being involved in plant response to stress, and regulating gene expression and cell signal transduction. UQ, particularly UQ10, has also been widely used in people’s life. It is effective in treating cardiovascular diseases, chronic gingivitis and periodontitis, and shows favorable impact on cancer treatment and human reproductive health. PQ and UQ are made up of an active benzoquinone ring attached to a polyisoprenoid side chain. Biosynthesis of PQ and UQ is very complicated with more than thirty five enzymes involved. Their synthetic pathways can be generally divided into two stages. The first stage leads to the biosynthesis of precursors of benzene quinone ring and prenyl side chain. The benzene quinone ring for UQ is synthesized from tyrosine or phenylalanine, whereas the ring for PQ is derived from tyrosine. The prenyl side chains of PQ and UQ are derived from glyceraldehyde 3-phosphate and pyruvate through the 2-C-methyl-D-erythritol 4-phosphate pathway and/or acetyl-CoA and acetoacetyl-CoA through the mevalonate pathway. The second stage includes the condensation of ring and side chain and subsequent modification. Homogentisate solanesyltransferase, 4-hydroxybenzoate polyprenyl diphosphate transferase and a series of benzene quinone ring modification enzymes are involved in this stage. PQ exists in plants, while UQ widely presents in plants, animals and microbes. Many enzymes and their encoding genes involved in PQ and UQ biosynthesis have been intensively studied recently. Metabolic engineering of UQ10 in plants, such as rice and tobacco, has also been tested. In this review, we summarize and discuss recent research progresses in the biosynthetic pathways of PQ and UQ and enzymes and their encoding genes involved in side chain elongation and in the second stage of PQ and UQ biosynthesis. Physiological functions of PQ and UQ played in plants as well as the practical application and metabolic engineering of PQ and UQ are also included.

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“…Furthermore, CoQ influences the expression of a large number of genes whose products are involved in a number of metabolic processes (3,4).…”

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confidence: 99%

Polyisoprenoid Epoxides Stimulate the Biosynthesis of Coenzyme Q and Inhibit Cholesterol Synthesis

Bentinger

Tekle

Brismar

et al. 2008

Journal of Biological Chemistry

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In our search for compounds that up-regulate the biosynthesis of coenzyme Q (CoQ), we discovered that irradiation of CoQ with ultraviolet light results in the formation of a number of compounds that influence the synthesis of mevalonate pathway lipids by HepG2 cells. Among the compounds that potently stimulated CoQ synthesis while inhibiting cholesterol synthesis, derivatives of CoQ containing 1-4 epoxide moieties in their polyisoprenoid side chains were identified. Subsequently, chemical epoxidation of all-trans-polyprenols of different lengths revealed that the shorter farnesol and geranylgeraniol derivatives were without effect, whereas the longer derivatives of solanesol enhanced CoQ and markedly reduced cholesterol biosynthesis. In contrast, none of the modified trans-transpoly-cis-polyprenols exerted noticeable effects. Tocotrienol epoxides were especially potent in our system; those with one epoxide moiety in the side-chain generally up-regulated CoQ biosynthesis by 200 -300%, whereas those with two such moieties also decreased cholesterol synthesis by 50 -90%. Prolonged treatment of HepG2 cells with tocotrienol epoxides for 26 days elevated their content of CoQ by 30%. In addition, the levels of mRNA encoding enzymes involved in CoQ biosynthesis were also elevated by the tocotrienol epoxides. The site of inhibition of cholesterol synthesis was shown to be oxidosqualene cyclase. In conclusion, epoxide derivatives of certain all-trans-polyisoprenoids cause pronounced stimulation of CoQ synthesis and, in some cases, simultaneous reduction of cholesterol biosynthesis by HepG2 cells.

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Functional connections and pathways of coenzyme Q10‐inducible genes: An in‐silico study

Cited by 60 publications

References 46 publications

Effects of Ubiquinol-10 on MicroRNA-146a Expression In Vitro and In Vivo

Effects of Ubiquinol-10 on MicroRNA-146a Expression In Vitro and In Vivo

Plastoquinone and Ubiquinone in Plants: Biosynthesis, Physiological Function and Metabolic Engineering

Polyisoprenoid Epoxides Stimulate the Biosynthesis of Coenzyme Q and Inhibit Cholesterol Synthesis

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