Regulation of Expression and Function of Scavenger Receptor Class B, Type I (SR-BI) by Na+/H+ Exchanger Regulatory Factors (NHERFs)

Hu, Zhigang; Hu, Jie; Zhang, Zhonghua; Shen, Wen-Jun; Yun, C. Chris; Berlot, Catherine H.; Kraemer, Fredric B.; Azhar, Salman

doi:10.1074/jbc.m112.437368

Cited by 35 publications

(47 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5A, D). Na+/H+ exchanger regulatory factor 1 (NHERF1) downregulates SR-BI [27] but was not induced in the liver of SNTA/B2−/− mice (Fig. 5A).…”

Section: Resultsmentioning

confidence: 99%

“…Here, the effects of PDZK1 on SR-BI protein levels are independent of SR-BI’s C-terminus, and thus do not occur via the mechanism identified in vivo [52]. The C-terminal amino acids of SR-BI (EAKL) do not represent a class I PDZ binding motif needed for complex formation with syntrophins [4, 7, 27] and SNTA does not bind SR-BI.…”

Section: Discussionmentioning

confidence: 99%

“…SR-BI in hepatocytes is stabilized by forming a complex with the PDZ domains of PDZK1 while overexpression of Na + /H + exchanger regulatory factors (NHERFs) 1 and 2 downregulates SR-BI protein [7, 27]. NHERF1 is not altered in the liver of the null mice and PDZK1 protein is even induced in the liver tissue of the SNTA/B2−/− mice.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Hebel

Eisinger

Neumeier

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

The syntrophins alpha (SNTA) and beta 2 (SNTB2) are molecular adaptor proteins shown to stabilize ABCA1, an essential regulator of HDL cholesterol. Furthermore, SNTB2 is involved in glucose stimulated insulin release. Hyperglycemia and dyslipidemia are characteristic features of the metabolic syndrome, a serious public health problem with rising prevalence. Therefore, it is important to understand the role of the syntrophins herein. Mice deficient for both syntrophins (SNTA/B2−/−) have normal insulin and glucose tolerance, hepatic ABCA1 protein and cholesterol. When challenged with a HFD, wild type and SNTA/B2−/− mice have similar weight gain, adiposity, serum and liver triglycerides. Hepatic ABCA1, serum insulin and insulin sensitivity are normal while glucose tolerance is impaired. Liver cholesterol is reduced, and expression of SREBP2 and HMG-CoA-R is increased in the knockout mice. Scavenger receptor-BI (SR-BI) protein is strongly diminished in the liver of SNTA/B2−/− mice while SR-BI binding protein NHERF1 is not changed and PDZK1 is even induced. Knock-down of SNTA, SNTB2 or both has no effect on hepatocyte SR-BI and PDZK1 proteins. Further, SR-BI levels are not reduced in brown adipose tissue of SNTA/B2−/− mice excluding that syntrophins directly stabilize SR-BI. SR-BI stability is regulated by MAPK and phosphorylated ERK2 is induced in the liver of the knock-out mice. Blockage of ERK activity upregulates hepatocyte SR-BI showing that increased MAPK activity contributes to low SR-BI. Sphingomyelin which is well described to regulate cholesterol metabolism is reduced in the liver and serum of the knock-out mice while the size of serum lipoproteins is not affected. Current data exclude a major function of these syntrophins in ABCA1 activity and insulin release but suggest a role in regulating glucose uptake, ERK and SR-BI levels, and sphingomyelin metabolism in obesity.

show abstract

“…5A, D). Na+/H+ exchanger regulatory factor 1 (NHERF1) downregulates SR-BI [27] but was not induced in the liver of SNTA/B2−/− mice (Fig. 5A).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Hebel

Eisinger

Neumeier

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

show abstract

“…Membranes were incubated with either rabbit anti-SR-BI or mouse anti-GAPDH (Santa Cruz Biotech) antibodies for 2 h. SR-BI polyclonal antibody was raised against a peptide to the C terminus of rat SR-BI (amino acids 489-509, AYSESLMSPAAKGTVLEQEAKL) (Hu et al, 2013). After three washes with Tris-buffered saline containing 0.1% Tween 20, the membranes were incubated with IRDye Ò 800CW goat antirabbit or IRDye Ò 6800LT goat antimouse secondary antibodies (LI-COR Biosciences) for 1.5 h. Proteins were detected with the Odyssey Ò Infrared Imaging System (LI-COR Biosciences).…”

Section: Western Blottingmentioning

confidence: 99%

“…The protein but not mRNA level of hepatic SR-BI, however, is primarily regulated post-transcriptionally through protein-protein interaction with PDZK1/NHERF3 (Ikemoto et al, 2000;Kocher and Krieger, 2009). We previously showed that two other NHERF family members, NHERF1 and NHERF2, negatively regulate the protein level of SR-BI in steroidogenic cells (Hu et al, 2013). repress the SR-BI expression through directly binding to the 3¢ UTR of SR-BI mRNA (Hu et al, 2012;Wang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I

Kuang

et al. 2016

DNA and Cell Biology

Self Cite

View full text Add to dashboard Cite

Regulation of HDL Genes: Transcriptional, Posttranscriptional, and Posttranslational

Kardassis

Gafencu

Zannis

et al. 2014

High Density Lipoproteins

View full text Add to dashboard Cite

HDL regulation is exerted at multiple levels including regulation at the level of transcription initiation by transcription factors and signal transduction cascades; regulation at the posttranscriptional level by microRNAs and other noncoding RNAs which bind to the coding or noncoding regions of HDL genes regulating mRNA stability and translation; as well as regulation at the posttranslational level by protein modifications, intracellular trafficking, and degradation. The above mechanisms have drastic effects on several HDL-mediated processes including HDL biogenesis, remodeling, cholesterol efflux and uptake, as well as atheroprotective functions on the cells of the arterial wall. The emphasis is on mechanisms that operate in physiologically relevant tissues such as the liver (which accounts for 80% of the total HDL-C levels in the plasma), the macrophages, the adrenals, and the endothelium. Transcription factors that have a significant impact on HDL regulation such as hormone nuclear receptors and hepatocyte nuclear factors are extensively discussed both in terms of gene promoter recognition and regulation but also in terms of their impact on plasma HDL levels as was revealed by knockout studies. Understanding the different modes of regulation of this complex lipoprotein may provide useful insights for the development of novel HDL-raising therapies that could be used to fight against atherosclerosis which is the underlying cause of coronary heart disease.

show abstract

Regulation of Expression and Function of Scavenger Receptor Class B, Type I (SR-BI) by Na+/H+ Exchanger Regulatory Factors (NHERFs)

Cited by 35 publications

References 90 publications

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I

Regulation of HDL Genes: Transcriptional, Posttranscriptional, and Posttranslational

Contact Info

Product

Resources

About