Protein kinase C α modulates liver X receptor α transactivation

Delvecchio, Christopher J.; Capone, John P.

doi:10.1677/joe-07-0525

Cited by 29 publications

(18 citation statements)

References 41 publications

(45 reference statements)

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“…Similarly, some reports demonstrated that activation of protein kinase A and protein kinase C decreased LXR␣ target gene expressions (39,41), and our previous report suggested that SIK1 can regulate hepatic lipogenesis by controlling SREBP-1c phosphorylation (26). However, the histone deacetylase Sirt1 has been shown to positively regulate LXR␣ target gene expression (18).…”

Section: Discussionmentioning

confidence: 75%

Orphan Nuclear Receptor DAX-1 Acts as a Novel Corepressor of Liver X Receptor α and Inhibits Hepatic Lipogenesis

Nedumaran

Kim

Hong

et al. 2010

Journal of Biological Chemistry

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DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is a member of the nuclear receptor superfamily that can repress diverse nuclear receptors and has a key role in adreno-gonadal development. Our previous report has demonstrated that DAX-1 can inhibit hepatocyte nuclear factor 4␣ transactivity and negatively regulate glu Nuclear receptors are a class of DNA binding transcription factors that regulate gene expression and play important roles in a variety of biological and pathological processes (2). Orphan nuclear receptor DAX-1 (NROB1) is an unusual member of the nuclear receptor superfamily (3). The C-terminal region has the structure that is characteristic of a ligand binding domain (LBD).5 Unlike other nuclear receptors, the N-terminal region does not have any classical DNA binding domain. However, it has three short repeats (65-67 amino acids) each containing an LXXLL-related motif. Duplication of the DAX-1 gene is associated with male to female reversal in XY individuals, and mutations in DAX-1 are responsible for adrenal hypoplasia congenita, an inherited disorder of adrenal gland development (4). DAX-1 generally acts as a negative regulator to repress the transcriptional activity of receptors such as estrogen receptor, thyroid receptor ␤, steroidogenic factor (SF-1), androgen receptor, estrogen receptor-related receptor ␥, glucocorticoid receptor, nerve growth factor-inducible gene B (Nur77), and peroxisome proliferator-activated receptor ␥ (PPAR␥) (5-12). We have previously reported that DAX-1 can negatively regulate the expression of gluconeogenic genes by inhibiting the transcriptional activity of hepatocyte nuclear factor 4 ␣ (HNF4␣) (1). DAX-1 is also known to interact with and inhibit the transcriptional activity of transcription factors, including OCT3/4 (13). DAX-1 has been shown to compete with nuclear receptor coactivators such as PGC-1␣ (11), GRIP-1 (10), and SRC-1 (11), and it is also known to recruit corepressors such as NCoR and Alien (9). A recent report showing the three-dimensional structure of DAX-1 reveals that Dax-1 could function as a ligand-independent nuclear receptor as well as a competitive transcriptional corepressor (14).Liver X receptor ␣ (LXR␣) is a member of the nuclear receptor superfamily that heterodimerizes with retinoid X receptor (RXR). LXR␣/RXR heterodimers bind to DR-4-type response elements known as the LXR-response elements (LXRE) in their target genes. LXR␣ is abundantly expressed in tissues with *

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Section: Discussionmentioning

confidence: 75%

Orphan Nuclear Receptor DAX-1 Acts as a Novel Corepressor of Liver X Receptor α and Inhibits Hepatic Lipogenesis

Nedumaran

Kim

Hong

et al. 2010

Journal of Biological Chemistry

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“…An increase in the expression of CD11b on THP-1 cells treated with PMA for 2 days was observed by flow cytometric and western blotting analysis while the expression of ABCA1 decreased from day 1 to day 5 (Supplementary Figure 3). PMA is presumed to have reduced the ABCA1 gene expression via PKC activation [29], since PKC was activated with PMA as stated above. Taken together, these results suggest that variously differentiated cells were prepared.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1 Cells

et al. 2016

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Apolipoprotein A-I (apoA-I), the main protein component of high-density lipoprotein (HDL), has many protective functions against atherosclerosis, one of them being cholesterol efflux capacity. Although cholesterol efflux capacity measurement is suggested to be a key biomarker for evaluating the risk of development of atherosclerosis, the assay has not been optimized till date. This study aims at investigating the effect of different states of cells on the cholesterol efflux capacity. We also studied the effect of apoA-I modification by homocysteine, a risk factor for atherosclerosis, on cholesterol efflux capacity in different states of cells. The cholesterol efflux capacity of apoA-I was greatly influenced by the extent of differentiation of THP-1 cells and attenuated by excessive foam cell formation. N-Homocysteinylated apoA-I indicated a lower cholesterol efflux capacity than normal apoA-I in the optimized condition, whereas no significant difference was observed in the cholesterol efflux capacity between apoA-I in the excessive cell differentiation or foam cell formation states. These results suggest that cholesterol efflux capacity of apoA-I varies depending on the state of cells. Therefore, the cholesterol efflux assay should be performed using protocols optimized according to the objective of the experiment.

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“…The precise roles of individual PKC isoforms will clearly require analysis of the effect of 22-(R)-HC and 9cRA on the activities of individual members along with the effect of their knockdown or knockout on the various cellular responses. The role of PKCa in the regulation of transactivation of LXRa has been previously investigated though these studies were not in macrophages [Delvecchio and Capone, 2008]. Thus, transactivation by LXR was decreased by activation of PKC in monkey kidney COS-1 cells, human embryonic kidney HEK293 cell line and human hepatocellular carcinoma HepG2 cell line [Delvecchio and Capone, 2008].…”

Section: Discussionmentioning

confidence: 97%

Protein Kinase C Is Involved in the Induction of ATP‐Binding Cassette Transporter A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human Macrophages

Huwait

Singh

Michael

et al. 2015

J of Cellular Biochemistry

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The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression. Protein kinase C (PKC) is often found to regulate the action of nuclear receptors and cross talk between this kinase family and JNK and/or PI3K has been shown in several settings. We have, therefore, investigated a potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found to attenuate the induction of ABCA1 protein expression, the activation of the JNK signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed further by the use of more isotype-specific inhibitors. These studies, therefore, reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA in human macrophages.

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Protein kinase C α modulates liver X receptor α transactivation

Cited by 29 publications

References 41 publications

Orphan Nuclear Receptor DAX-1 Acts as a Novel Corepressor of Liver X Receptor α and Inhibits Hepatic Lipogenesis

Orphan Nuclear Receptor DAX-1 Acts as a Novel Corepressor of Liver X Receptor α and Inhibits Hepatic Lipogenesis

Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1 Cells

Protein Kinase C Is Involved in the Induction of ATP‐Binding Cassette Transporter A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human Macrophages

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