Zou, D. | Search bioRxiv

bioRxiv2020

Hesperetin inhibits foam cell formation in macrophages via activating LXRα signal in an AMPK dependent manner

Cholesterol efflux from macrophages is the first step of cholesterol reverse transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Liver X receptor alpha (LXR) and adenosine monophosphate activated protein kinases (AMPK) both have the pivotal role in cholesterol homeostasis. However the association between these two molecules in cell model of atherosclerosis is poorly understood. Hesperetin has been reported to possess several protective effects for cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism on macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin in cholesterol efflux by using human macrophage derived foam cells, focusing on liver X receptor alpha (LXR) and adenosine monophosphate activated protein kinases (AMPK) implication. Hesperetin treatment concentration-dependently reduced foam cell formation, intracellular cholesterol level and cholesterol esterification rate, and enhanced cholesterol efflux in THP-1 macrophages. Hesperetin upregulated the protein levels of LXR and its targets including ABCA1, ABCG1 as well as SR-BI, and phosphorylated-AMPK. Meanwhile, hesperetin-induced upregulation of LXR expression was enhanced by AMPK agonist and inhibited by AMPK inhibitor. Furthermore, hesperetin increased mRNA level of LXR and its target genes, all which were depressed by AMPK1/2 small interfering RNA (siRNA) transfection. In conclusion, we founded for the first time that hesperetin could active AMPK. And this activation upregulated LXR and its targets including ABCA1, ABCG1 and SR-BI, which significantly inhibited foam cell formation and promoted cholesterol efflux in THP-1 macrophages. Our results highlight the therapeutic potential of hespretin for the possible reduction in foam cell formation. This new mechanism could contribute the anti-atherogenic effects of hesperetin.

pharmacology and toxicology↗

bioRxiv2020

SnpReady for Rice (SR4R) Database

The information commons for rice (IC4R) database is a collection of [~]18 million SNPs (single nucleotide polymorphisms) identified by the resequencing of 5,152 rice accessions. Although IC4R offers ultra-high density rice variation map, these raw SNPs are not readily usable for the public. To satisfy different research utilizations of SNPs for population genetics, evolutionary analysis, association studies and genomic breeding in rice, the raw genotypic data of the 18 million SNPs were processed by unified bioinformatics pipelines. The outcomes were used to develop a daughter database of IC4R - SnpReady for Rice (SR4R). The SR4R presents four reference SNP panels, including 2,097,405 hapmapSNPs after data filtration and genotype imputation, 156,502 tagSNPs selected from linkage disequilibrium (LD)-based redundancy removal, 1,180 fixedSNPs selected from genes exhibiting selective sweep signatures, and 38 barcodeSNPs selected from DNA fingerprinting simulation. SR4R thus offers a highly efficient rice variation map that combines reduced SNP redundancy with extensive data describing the genetic diversity of rice populations. In addition, SR4R provides rice researchers with a web-interface that enables them to browse all four SNP panels, use online toolkits, and retrieve the original data and scripts for a variety of population genetics analyses on local computers. The SR4R is freely available to academic users at http://sr4r.ic4r.org/.

bioinformatics↗