Abstract:
:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is known to reduce hepatic low-density lipoprotein receptor (LDLR) levels and increase plasma LDL cholesterol. It is not clear, however, whether secreted PCSK9 degrades extrahepatic LDLRs. We present evidence that recombinant PCSK9, either injected intravenously into or expressed in the liver of C57BL/6 mice, significantly reduced LDLR levels in multiple extrahepatic tissues. During the initial characterization, we found that injected human recombinant PCSK9 at 30 microg/mouse had a half-life of 15 min in serum in mice. Hepatic LDLR levels were reduced within 30min and the degradation of hepatic LDLR reached the maximum 2h after the initial protein injection. Endocytosis of PCSK9 in liver occurred within 5min of protein injection and internalized PCSK9 was only barely detectable within 1h. When extrahepatic LDLRs were examined by Western blotting analysis, we found significant reductions of LDLRs in multiple extrahepatic tissues including lung, adipose and kidney along with the more dramatic reduction of LDLRs in liver. These studies were further extended using adenoviral expression of human PCSK9 in C57BL/6 mice to demonstrate that PCSK9 produced in liver impacted extrahepatic tissue LDLR levels as well. Taken together, our studies indicate that secreted PCSK9 can potentially impact extrahepatic tissue cholesterol homeostasis by regulating extrahepatic tissue LDLR levels.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Schmidt RJ,Beyer TP,Bensch WR,Qian YW,Lin A,Kowala M,Alborn WE,Konrad RJ,Cao Gdoi
10.1016/j.bbrc.2008.04.004subject
Has Abstractpub_date
2008-06-13 00:00:00pages
634-40issue
4eissn
0006-291Xissn
1090-2104pii
S0006-291X(08)00657-8journal_volume
370pub_type
杂志文章abstract::Intercellular spaces between adjacent mucosal epithelial cells are sealed by tight junctions (TJs) that prevent the free movement of solutes across the epithelium. Claudins (CLs), a family of 27 integral membrane proteins, are essential components for TJ seals. We previously used a CL-3/-4 binder, the C-terminal fragm...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2012.05.060
更新日期:2012-06-29 00:00:00
abstract::Dilated cardiomyopathy (DCM) is a condition whereby the normal muscular function of the myocardium is altered by specific or multiple aetiologies. About 25-35% of DCM patients show familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins. Most of the DCM-related mutations fall ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2011.12.136
更新日期:2012-02-10 00:00:00
abstract::It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT(3)) receptor to cause nausea and vomiting. In general, antagonist for 5-HT(3) receptor is used as anti-emetics during chemotherapy. However, we found that anti-cancer drug irinoteca...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2011.10.084
更新日期:2011-11-18 00:00:00
abstract::Most human cancers are of epithelial origin, but many cell culture models for the study of cancer-causing genes use fibroblasts. In addition, efficient delivery and stable expression of foreign genes into non-transformed cell lines are often difficult. To address both questions, we here established a non-transformed r...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2005.10.045
更新日期:2005-12-16 00:00:00
abstract::S-100 protein and annexin II2-p11(2) were reported to inhibit and to stimulate the assembly of glial fibrillary acidic protein (GFAP), respectively, in a Ca(2+)-dependent manner. Here we show by a number of experimental approaches that S-100 protein contrasts all the effects of annexin II2-p11(2) on GFAP assembly and,...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1995.1421
更新日期:1995-03-28 00:00:00
abstract::The nuclear enzyme poly(ADP-ribosyl) transferase (pADPRT) catalyzes the formation of poly(ADP-ribose) from NAD+. Several nuclear proteins and pADPRT itself are targets for the modification by poly(ADP-ribosyl)ation. It is demonstrated here that poly(ADP-ribose) or pADPRT automodified with poly(ADP-ribose) interacts no...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1999.0824
更新日期:1999-06-16 00:00:00
abstract::Upon binding of a Wnt to its receptor, GSK3beta is inhibited through an unknown mechanism involving Dishevelled (Dsh), resulting in the dephosphorylation and stabilization of beta-catenin, which translocates to the nucleus and interacts with Lef/Tcf transcription factors to activate target gene expression. Axin is a s...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1999.1760
更新日期:1999-12-09 00:00:00
abstract::Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferat...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2009.02.033
更新日期:2009-04-03 00:00:00
abstract::Antithrombin inhibits chemokine-induced migration of neutrophils by activating heparan sulfate proteoglycan-dependent signaling. Mechanisms of antithrombin's effects on neutrophils were, therefore, studied by testing function and expression of heparan sulfate proteoglycans in RT-PCR or flow cytometry and cell migratio...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.5534
更新日期:2001-09-14 00:00:00
abstract::Enterococcus faecalis (E. faecalis) infection is considered an important etiological factor for the development of persistent apical periodontitis (PAP), but the exact mechanisms of autophagy between E. faecalis and immune cells remain unknown. In this study, we elucidated how E. faecalis lipoteichoic acid (LTA) is as...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2018.03.109
更新日期:2018-04-15 00:00:00
abstract::A single nucleotide polymorphism (SNP) resulting in a substitution from Gln to His was found in exon 4 of the CYP2B6 gene in Japanese. The frequency of the variant allele was found to be 19.9%. The mutant- and the wild-type enzymes were expressed in Escherichia coli, and the effects of the single amino acid substituti...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.4524
更新日期:2001-03-01 00:00:00
abstract::The activity of neutral sphingomyelinase (EC 3.1.4.12) in a plasma membrane enriched fraction was found to be increased in dexamethasone treated cells. The elevation of sphingomyelinase activity was blocked by cycloheximide indicating that protein synthesis was required for the steroid action. Ceramidase (EC3.5.1.23) ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(90)92068-b
更新日期:1990-03-16 00:00:00
abstract::Protein Z was purified from rabbit liver cytosol by affinity chromatography on oleic acid-agarose and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After removal of sodium dodecyl sulfate, the renatured protein was found to bind heme and bilirubin with a Kd of approximately 1 microM which prod...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(85)91172-6
更新日期:1985-10-30 00:00:00
abstract::Protection against hypoxic injury by supraphysiological glycine and alanine concentrations was investigated in the isolated perfused rat kidney (IPRK). 23Na NMR detects consistent increases in total renal Na in IPRK during hypoxic perfusion. Increasing the concentration of glycine and alanine to 5 mM each produced a 3...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1994.2121
更新日期:1994-08-15 00:00:00
abstract::Mammalian cells contain two fatty acid synthesis pathways, the cytosolic FASI pathway, and the mitochondrial FASII pathway. The selection behind the conservation of the mitochondrial pathway is not completely understood, given the presence of the cytosolic FAS pathway. In this study, we show through heterologous gene ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2013.10.072
更新日期:2013-11-15 00:00:00
abstract::Many factors regulate the expression of specialised secondary metabolite biosynthetic gene clusters, which have been recognised as important for the discovery of novel microbial natural products. A cosmid library based on genomic DNA of the marine-derived Streptomyces puniceus Act1085 was constructed and screened to i...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2017.06.098
更新日期:2017-08-26 00:00:00
abstract::The VLDL (very low-density lipoprotein) receptor is a peripheral lipoprotein receptor expressing in fatty acid active tissues abundantly. In the Balb/c fasting mice, VLDL receptor as well as LPL (lipoprotein lipase), FAT (fatty acid translocase)/CD36, H-FABP (heart-type fatty acid-binding protein), ACS (acyl-CoA synth...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/S0006-291X(02)00323-6
更新日期:2002-05-10 00:00:00
abstract::Multidrug resistance protein 1 (MRP1) is a member of the ATP-binding cassette superfamily. Using the energy provided by ATP hydrolysis, it transports a broad spectrum of substrates across the plasma membrane, including hormones, leukotriene C(4), bile salts, and anti-cancer drugs. Recent works have suggested that P-gl...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2007.02.075
更新日期:2007-04-20 00:00:00
abstract::The effect of thyroid-stimulating hormone receptor (TSHR) on hepatic lipid accumulation in vivo is not fully understood. Further, while TSHR in the thyroid has been studied extensively, whether and how the absence of TSHR in the liver affects systemic energy metabolism has not yet been reported. To examine these effec...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2018.01.187
更新日期:2018-02-26 00:00:00
abstract:BACKGROUND:The functionality of lncRNA snaR has only been characterized in breast cancer and colon cancer. The aim of the current study is to explore the involvement of lncRNA snaR in ovarian carcinoma (OC). MATERIALS AND METHODS:Expression of lncRNA snaR and GRB2-associated binding protein 2 (GAB2) in plasma of both ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2018.07.152
更新日期:2018-09-10 00:00:00
abstract::By radiolabeling using NaIO4/[3H]KBH4, a new sialoglycoprotein with Mr of 19,000 was found in the secretion of rat seminal vesicle. It was shown to interact non-covalently with semen coagulum. It existed in three acidic forms with pI values of 4.1, 3.7 and 2.9 and possessed high contents of sialic acids and acidic ami...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(86)90503-6
更新日期:1986-04-29 00:00:00
abstract::Kaposi sarcoma and primary effusion lymphoma cells are infected with Kaposi sarcoma-associated herpesvirus (KSHV), predominantly in the latent form, and KSHV replication is observed rarely. Angiogenesis plays a crucial role in the pathogenesis of both Kaposi sarcoma and primary effusion lymphoma. In this study, we fou...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2015.06.100
更新日期:2015-08-07 00:00:00
abstract::An altered metabolism supports growth of tumor. AKT, a major signal integrator plays a key role in cell metabolism. We have shown that nutritional deprivation activates AKT as observed by increased phosphorylation of both Thr308 and Ser473. Pharmacological inhibition or silencing of AKT by siRNA affects cell viability...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2016.02.064
更新日期:2016-03-18 00:00:00
abstract::pp120, a plasma membrane glycoprotein, is phosphorylated on Tyr488 by the insulin receptor tyrosine kinase. This requires basal phosphorylation on Ser503 by cAMP-dependent serine kinase. Phe513, the other tyrosine residue in the intracellular domain, does not undergo insulin-stimulated phosphorylation. Phe488 mutation...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.8822
更新日期:1998-06-18 00:00:00
abstract::Extracellular superoxide dismutase (EC-SOD) is the major isozyme of SOD in arteries, but is also abundant in lungs. In particular, mouse lungs contain large amounts of EC-SOD compared to lungs in other mammals. This suggests that EC-SOD may have an amplified function in the mouse lung. This study describes the purific...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2000.3327
更新日期:2000-08-28 00:00:00
abstract::Laser Doppler velocimetry measurements on purple membrane suspensions from Halobacterium halobium showed a linear correlation between electrophoretic mobility and applied electric field, electrokinetic responses could be rapidly monitored. Native membranes are less charged than white membrane preparations (from the R1...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(84)90467-4
更新日期:1984-07-18 00:00:00
abstract::Our previous study on the dynamic transcriptomes activated during human erythropoiesis suggested that transcription factor forkhead box O3 (FOXO3) possibly plays a role in erythroid differentiation. Functional studies in human cell line TF-1 indicated that FOXO3 knockdown repressed erythropoietin (EPO)-induced erythro...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2015.03.128
更新日期:2015-05-15 00:00:00
abstract::Serine416 of human tau protein is believed to be phosphorylated in Alzheimer neurofibrillary tangles. We synthesized a fragment of tau, consisting of amino acids 408-421 in both non-phosphorylated and serine416-phosphorylated forms. Circular dichroism in a trifluoroethanol-water mixture indicated a beta-turn----beta-p...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(05)80112-3
更新日期:1992-01-15 00:00:00
abstract::A combination of the RT-PCR method and subsequent screening of the cDNA library of mouse skeletal muscle with the cDNA isolated by RT-PCR used as a probe led to isolation of cDNAs encoding a polypeptide (mSim) with bHLH and PAS domains which show high similarity to the corresponding regions of Drosophila Sim, a master...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1996.0104
更新日期:1996-01-17 00:00:00
abstract::The narrow leaf1 (nal1) mutant of rice (Oryza sativa L.) exhibits a narrow leaf phenotype. Previous studies have shown that NAL1 modulates leaf size by affecting vein patterning and cell division; however, the underlying mechanism remains unclear. Here, we report that the nal1 mutant shows reduced size of the leaf aba...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2019.06.142
更新日期:2019-08-27 00:00:00