Analysis of Adiponectin Gene Polymorphisms in Chinese Population with Systemic Lupus Erythematosus

Fang, Wen Liang; Zhou, Bin; Wang, Yan Yun; Chen, Yu; Zhang, Lin

doi:10.1155/2010/401537

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…We decided to base our assay for investigating ligand-AdipoR1 interactions on the first protein-protein interaction of AdipoR1 that is known to trigger downstream signaling underlying the anti-diabetic and cardioprotective effects of adiponectin, i.e. the interaction between AdipoRs and the coupling protein APPL1 (Figure 1) [43], [53]. The split luciferase assay could possibly be optimized further by controlling relative expression levels of AdipoR1 and APPL1, for example, by expressing them from promoters regulated by different stimuli.…”

Section: Discussionmentioning

confidence: 99%

A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

et al. 2013

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Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc) activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc) in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p). The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides’ ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA) signaling and AMP activated protein kinase (AMPK) phosphorylation in S. cerevisiae, which are homologous to important mammalian adiponectin-AdipoR1 signaling pathways. This system should facilitate the development of therapeutic inventions targeting adiponectin and/or AdipoR physiology.

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Section: Discussionmentioning

confidence: 99%

A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

et al. 2013

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“…Several studies in various populations in Africa (dbSNP database, 2011), Asia (Fang et al, 2010;Kang et al, 2005;Li et al, 2007;Sun et al, 2008;dbSNP database, 2011), Europe [Cesari et al, 2007;José et al, 2006;Panidis et al, 2004;dbSNP database, 2011;Szopa et al, 2009;Ukkola et al, 2003), and America (Kaklamni et al, 2008a,b;dbSNP database, 2011) have been conducted to determine ADIPOQ and ADIPOR2 alleles and genotype frequencies. This study aimed to investigate these genes in Iranian population and compare our findings to other populations.…”

Section: Introductionmentioning

confidence: 99%

Distribution and genotype frequency of adiponectin (+45 T/G) and adiponectin receptor2 (+795 G/A) single nucleotide polymorphisms in Iranian population

Namvaran

Azarpira

Geramizadeh

et al. 2011

Gene

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“…Adiponectin gene polymorphisms are not associated with SLE risk, 106 but high levels of adiponectin have been reported in SLE patients with and without lupus nephritis. Correlations with disease activity are however contradictory.…”

Section: Tions In Addition To Its Effects On T Cells Leptin Activatmentioning

confidence: 98%

Metabolic determinants of lupus pathogenesis

Teng

Brown

Choi

et al. 2020

Immunological Reviews

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The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4 + T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues. K E Y W O R D Sglucose, glutamine, lupus, metabolic inhibitors, metabolism

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Analysis of Adiponectin Gene Polymorphisms in Chinese Population with Systemic Lupus Erythematosus

Cited by 7 publications

References 29 publications

A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

Distribution and genotype frequency of adiponectin (+45 T/G) and adiponectin receptor2 (+795 G/A) single nucleotide polymorphisms in Iranian population

Metabolic determinants of lupus pathogenesis

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