Binding of Hepatitis B Virus Pre-S1 Domain-Derived Synthetic Myristoylated Peptide to Scavenger Receptor Class B Type 1 with Differential Properties from Sodium Taurocholate Cotransporting Polypeptide

(1) Background: The myristoylated pre-S1 peptide (Myr47) synthesized to mimic pre-S1 domain (2-48) in large (L) surface protein of hepatitis B virus (HBV) prevents HBV infection to hepatocytes by binding to sodium taurocholate cotransporting polypeptide (NTCP). We previously demonstrated that yeast-derived nanoparticles containing L protein (bio-nanocapsules: BNCs) bind scavenger receptor class B type 1 (SR-B1). In this study, we examined the binding of Mry47 to SR-B1. (2) Methods: The binding and endocytosis of fluorescence-labeled Myr47 to SR-B1 (and its mutants)-green fluorescence protein (GFP) fusion proteins expressed in HEK293T cells were analyzed using flow cytometry and laser scanning microscopy (LSM). Various ligand-binding properties were compared between SR-B1-GFP and NTCP-GFP. Furthermore, the binding of biotinylated Myr47 to SR-B1-GFP expressed on HEK293T cells was analyzed via pull-down assays using a crosslinker and streptavidin-conjugated beads. (3) Conclusions: SR-B1 bound not only Myr47 but also its myristoylated analog and BNCs, but failed to bind a peptide without myristoylation. However, NTCP only bound Myr47 among the ligands tested. Studies using SR-B1 mutants suggested that both BNCs and Myr47 bind to similar sites of SR-B1. Crosslinking studies indicated that Myr47 binds preferentially SR-B1 multimer than monomer in both HEK293T and HepG2 cells.

Targeted Therapy of Atherosclerosis Vulnerable Plaque By ROS-Scavenging Nanoparticles And MR/Fluorescence Dual-Modality Imaging Tracing

Background: Cardiovascular diseases are currently the leading cause of death and disability worldwide, and the key pathological basis is atherosclerosis (AS). Especially, the rupture of vulnerable plaques is the main cause of acute cardiovascular and cerebrovascular events such as myocardial infarction and stroke. Thus, the early identifying and therapy of vulnerable plaques are necessary. Results: In this study, we developed a novel multimodal imaging platform (GPRD) based on Gd doped Prussian blue (GPB) and rhodamine (Rd) to specifically target and identify the vulnerable plaques with the help of dextran sulfate (DS), one of the excellent ligands of scavenger receptor class A (SR-A). It is more important that the nano-enzyme capacity of GPRD NPs realized the elimination of the excessive production of ROS in cells, and the following reduction of ROS-induced oxidative stress, inflammation, apoptosis, and the formation of macrophage-derived foam cells, presenting an inhibition of plaque progress eventually. Conclusions: The ROS-scavenging multimodal imaging nanoprobe provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.

Differential expression of scavenger receptor class A member 5 in cancers of the breast.

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding scavenger receptor class A member 5, SCARA5, when comparing primary tumors of the breast to the tissue of origin, the normal breast. SCARA5 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of SCARA5 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with basal-like and normal-like subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. SCARA5 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.

Tumor suppressive effect of scavenger receptor class A member 5 overexpression in colorectal cancer by regulating PI3K/AKT/mTOR pathway

Background Colorectal cancer (CRC) exhibits high risks of morbidity and mortality. Objective To investigate the effect of scavenger receptor class A member 5 (SCRAR5) on CRC and its mechanism on modulation of cancer development. Methods The SCRAR5 expression in four kinds of CRC cell lines (SW620, SW480, HT29, and HCT116) was measured by quantitative PCR and western blotting, respectively. The effects of SCRAR5 abnormal expression on cell proliferation, apoptosis, and migration were analyzed by CCK-8 assay, EdU assay, colony-forming assay, flow cytometry assay, Transwell assay and wound healing assay, respectively. Meanwhile, the involvements of PI3K/AKT/mTOR pathway with the role of SCRAR5 were investigated by western blotting. Afterwards, the in vivo effects of SCRAR5 abnormal expression on CRC xenograft mice were finally investigated by evaluating tumor volume, apoptosis and Ki67 expression. Results SCRAR5 was lowly expressed in CRC cell lines, especially SW480 cells. Up-regulation of SCRAR5 significantly promoted cell apoptosis, reduced cell proliferation and migration in SW480 cells. Notably, SCRAR5 overexpression obviously inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Reversely, SCRAR5 silence exhibited promoting effects on HT29 cells. Consistently, in vivo experiments also revealed that SCRAR5 overexpression remarkably suppressed tumor volume and Ki67 expression, as well as promoted cell apoptosis. Conclusions Overall, up-regulating of SCRAR5 obviously inhibited CRC tumor growth in vitro and in vivo, which might be related to PI3K/AKT/mTOR pathway.