Isolation of pig mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene promoter: characterization of a peroxisome proliferator-responsive element

Ortiz, J. A.; Mallolas, Judith; Nicot, Carine; Bofarull, Josep; Rodríguez, Joaquín; Hegardt, Fausto G.; Haro, Diego; Marrero, Pedro F.

doi:10.1042/bj3370329

Cited by 16 publications

(6 citation statements)

References 47 publications

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“…We found that a PKA inhibitor did not influence SAA reduced perilipin promoter PPRE activity, suggesting that the effect of SAA reduced PPRE activity of perilipin is not from PKA. The porcine perilipin PPRE DNA sequence is an imperfect direct repeat‐1 element similar to what was shown previously (28). Therefore, we speculate that SAA‐induced lipolysis is due to a marked reduction in perilipin protein content, and enhanced lipase activity.…”

Section: Discussionsupporting

confidence: 71%

Serum Amyloid A Induces Lipolysis by Downregulating Perilipin Through ERK1/2 and PKA Signaling Pathways

Liu

Lin

Chen

et al. 2011

Obesity

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Serum amyloid A (SAA) is not only an apolipoprotein, but also a member of the adipokine family with potential to enhance lipolysis. The purpose of this study was to explore how SAA facilitates lipolysis in porcine adipocytes. We found that SAA increased the phosphorylation of perilipin and hormone‐sensitive lipase (HSL) after 12‐h treatment and decreased perilipin expression after 24‐h treatment, and these effects were prevented by extracellular signal‐regulated kinase (ERK) or protein kinase A (PKA) inhibitors in primary adipocyte cell culture. SAA treatment decreased HSL and adipose triglyceride lipase (ATGL) expression. SAA treatment also activated ERK and PKA by increasing the phosphorylation of these kinases. Moreover, SAA significantly increased porcine adipocyte glycerol release and lipase activity, which was inhibited by either ERK (PD98059) or PKA (H89) inhibitors, suggesting that ERK and PKA were involved in mediating SAA enhanced lipolysis. SAA downregulated the expression of peroxisome proliferator‐activated receptor γ (PPARγ) mRNA, which was reversed by the ERK inhibitor. We performed a porcine perilipin promoter assay in differentiated 3T3–L1 adipocytes and found that SAA reduced the porcine perilipin promoter specifically through the function of its PPAR response element (PPRE), and this effect was reversed by the ERK inhibitor. These findings demonstrate that SAA‐induced lipolysis is a result of downregulation of perilipin and activation of HSL via ERK/PPARγ and PKA signaling pathways. The finding could lead to developing new strategies for reducing human obesity.

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Section: Discussionsupporting

confidence: 71%

Serum Amyloid A Induces Lipolysis by Downregulating Perilipin Through ERK1/2 and PKA Signaling Pathways

Liu

Lin

Chen

et al. 2011

Obesity

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“…However, the Sp1-binding site has also been reported to participate in Miz-1-mediated transactivation (38). The HMGCS2 transcription start site has been established by primer extension, S1 nuclease protection, and rapid amplification of cDNA ends experiments in rat (11), pig (41), and human (15) genes and does not contain a canonical Inr sequence. Mutation of critical elements in the HMGCS2 proximal promoter diminished its transcriptional activity and therefore hinders the study of Myc transrepression.…”

Section: Discussionmentioning

confidence: 99%

Ketogenic HMGCS2 Is a c-Myc Target Gene Expressed in Differentiated Cells of Human Colonic Epithelium and Down-Regulated in Colon Cancer

Camarero

Mascaró

Mayordomo

et al. 2006

Molecular Cancer Research

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HMGCS2, the gene that regulates ketone body production, is expressed in liver and several extrahepatic tissues, such as the colon. In CaCo-2 colonic epithelial cells, the expression of this gene increases with cell differentiation. Accordingly, immunohistochemistry with specific antibodies shows that HMGCS2 is expressed mainly in differentiated cells of human colonic epithelium. Here, we used a chromatin immunoprecipitation assay to study the molecular mechanism responsible for this expression pattern. The assay revealed that HMGCS2 is a direct target of c-Myc, which represses HMGCS2 transcriptional activity. c-Myc transrepression is mediated by blockade of the transactivating activity of Miz-1, which occurs mainly through a Sp1-binding site in the proximal promoter of the gene. Accordingly, the expression of human HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. HMGCS2 protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors. Based on these findings, we propose that ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2.

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“…In vitro studies using cell cultures have demonstrated that CLA acts as an agonist of the peroxisome proliferator activated receptor family (PPAR). PPARs are DNA binding transcription factors that bind the peroxisome proliferator repeat element (PPRE) (2, 3, 4) as a heterodimer with the retinoic acid receptor (RxR), which is activated by 9-cis-retinoic acid (vitamin A) (5, 6). The PPAR family is currently divided into three subgroups, α, β and γ. PPARβ is expressed throughout the body and is involved in embryo development (7, 8).…”

Section: Introductionmentioning

confidence: 99%

A semi-quantitative RT-PCR method to measure thein vivo effect of dietary conjugated linoleic acid on porcine muscle PPAR gene expression

Meadus

2003

Biol. Proced. Online

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Conjugated linoleic acid (CLA) can activate (in vitro) the nuclear transcription factors known as the peroxisome proliferators activated receptors (PPAR). CLA was fed at 11 g CLA/kg of feed for 45d to castrated male pigs (barrows) to better understand long term effects of PPAR activation in vivo. The barrows fed CLA had lean muscle increased by 3.5% and overall fat reduced by 9.2% but intramuscular fat (IMF %) was increased by 14% (P < 0.05). To measure the effect of long term feeding of CLA on porcine muscle gene expression, a semi-quantitative RT-PCR method was developed using cDNA normalized against the housekeeping genes cyclophilin and β-actin. This method does not require radioactivity or expensive PCR instruments with real-time fluorescent detection. PPARγ and the PPAR responsive gene AFABP but not PPARα were significantly increased (P < 0.05) in the CLA fed pig's muscle. PPARα and PPARγ were also quantitatively tested for large differences in gene expression by western blot analysis but no significant difference was detected at this level. Although large differences in gene expression of the PPAR transcriptional factors could not be confirmed by western blotting techniques. The increased expression of AFABP gene, which is responsive to PPAR transcriptional factors, confirmed that dietary CLA can induce a detectable increase in basal PPAR transcriptional activity in the live animal.

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Isolation of pig mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene promoter: characterization of a peroxisome proliferator-responsive element

Cited by 16 publications

References 47 publications

Serum Amyloid A Induces Lipolysis by Downregulating Perilipin Through ERK1/2 and PKA Signaling Pathways

Serum Amyloid A Induces Lipolysis by Downregulating Perilipin Through ERK1/2 and PKA Signaling Pathways

Ketogenic HMGCS2 Is a c-Myc Target Gene Expressed in Differentiated Cells of Human Colonic Epithelium and Down-Regulated in Colon Cancer

A semi-quantitative RT-PCR method to measure thein vivo effect of dietary conjugated linoleic acid on porcine muscle PPAR gene expression

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