Towards Investigating the Role of Proprotein Convertase Subtilisin/Kexin Family (PCSK/7/9) in Cancer by Using Bioinformatics Motif Detection Technique

2021 ◽  
Author(s):  
Umar Draz ◽  
Sana Yasin ◽  
Shafiq Hussain ◽  
Zaid Bin Faheem ◽  
Sarah Gul ◽  
...  
Keyword(s):  
Detection Technique ◽  
Proprotein Convertase ◽  
Motif Detection

Abstract 14315: New Insights Into the Mechanisms of Sepsis: The Role of Proprotein Convertase Subtilisin/kexin Type 9 as a Key Regulator of Pathogen Toxin Clearance

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Elena Topchiy ◽  
Yingjin Wang ◽  
John Boyd ◽  
Keith R Walley
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Ex Vivo ◽  
Fluorescent Microscopy ◽  
Hepatic Uptake ◽  
Cardiovascular Complications ◽  
Proprotein Convertase ◽  
Bacterial Endotoxins ◽  
Visceral Adipose

Background: To prevent severe inflammation during infection, the patient must quickly clear bacterial endotoxins from the circulation before they accumulate and are able to interact with immune cells and vascular endothelium, and induce inflammatory organ failure. Bacterial endotoxins are carried within lipoprotein particles. Thus, one mechanism of action for sepsis treatments could be acceleration of lipoprotein clearance by adipocytes and hepatocytes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases the rate of lipoprotein clearance. We have recently reported that reduced function of PCSK9 improves outcome and prevents cardiovascular complications associated with sepsis. Hypothesis: PCSK9 inhibits LDL associated LPS clearance through hepatic LDLR and VLDL associated LPS clearance through adipose VLDLR. Methods and Results: Using siRNA against the LDLR in HepG2 hepatocytes decreased uptake of fluorescently labeled LPS (fLPS) after 48 hours by 1.50±0.10 fold (n=3, p<0.05). Addition of recombinant PCSK9 in the absence of LDLR did not alter uptake of LPS. We confirmed that hepatic uptake of LPS is exclusively via the LDLR by fluorescent microscopy of ex vivo LPS treated primary hepatocytes isolated from LDLR -/- mice. To address the importance of the LDLR upon clearance of LPS from plasma, we injected fLPS into the portal vein of LDLR-/-, PCSK9-/- and wild type mice (WT). Compared to WT, LDLR-/- mice had 36±13% (n=9, p<0.001) increase in plasma LPS after 1 hour, whereas PCSK9-/- show a significant decrease (28±4%, n=9, p<0.001) in plasma LPS. LDLR-/-, but not PCSK9-/- mice showed 46±7% decrease (n=10, p<0.05) in hepatic uptake. On the other hand, compared to the WT PCSK9-/- mice had 200±35% (n=8, p<0.001) increase in LPS uptake by visceral adipose tissue whereas LDLR-/- had no effect compared to WT mice. To further investigate LPS uptake by adipose tissue we injected flLPS into the tail vein of VLDLR-/- and WT mice. VLDLR-/- mice had 33±6% (n=10, p<0.001) decrease in visceral adipose tissue uptake, with no significant change in hepatic uptake. Conclusions: Expression of hepatic LDLR and adipose VLDLR is mainly regulated by PCSK9 and both play important role in clearing LPS from circulation.

scholarly journals The Role of a Proprotein Convertase Inhibitor in Reactivation of Tumor-Associated Macrophages and Inhibition of Glioma Growth

2020 ◽  
Vol 17 ◽  
pp. 31-46
Author(s):  
Mélanie Rose ◽  
Marie Duhamel ◽  
Soulaimane Aboulouard ◽  
Firas Kobeissy ◽  
Emilie Le Rhun ◽  
...  
Keyword(s):  
Proprotein Convertase ◽  
Tumor Associated Macrophages ◽  
Glioma Growth

scholarly journals The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia

Circulation ◽  
2016 ◽  
Vol 134 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Mary E. Haas ◽  
Amy E. Levenson ◽  
Xiaowei Sun ◽  
Wan-Hui Liao ◽  
Joseph M. Rutkowski ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Proprotein Convertase

scholarly journals Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

2005 ◽  
Vol 102 (31) ◽  
pp. 11047-11052 ◽  
Author(s):  
Q. Qiu ◽  
A. Basak ◽  
M. Mbikay ◽  
B. K. Tsang ◽  
A. Gruslin
Keyword(s):  
Proprotein Convertase ◽  
Placental Development

Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia

2017 ◽  
Vol 108 ◽  
pp. 394-403 ◽  
Author(s):  
Sahir Sultan Alvi ◽  
Irfan A. Ansari ◽  
Imran Khan ◽  
Johar Iqbal ◽  
M. Salman Khan
Keyword(s):  
Potential Role ◽  
Proprotein Convertase

scholarly journals Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia

2011 ◽  
Vol 121 (9) ◽  
pp. 397-403 ◽  
Author(s):  
Martijn C.G.J. Brouwers ◽  
Marleen M.J. van Greevenbroek ◽  
Jason S. Troutt ◽  
Angela Bonner Freeman ◽  
Ake Lu ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Significant Rise ◽  
Low Density ◽  
Proprotein Convertase ◽  
Once Daily ◽  
Heritable Trait ◽  
The Relationship

The aim of the present study was to investigate the relationship between circulating PCSK9 (proprotein convertase subtilisin kexin type 9) and FCHL (familial combined hyperlipidaemia) and, when positive, to determine the strength of its heritability. Plasma PCSK9 levels were measured in FCHL patients (n=45), NL (normolipidaemic) relatives (n=139) and their spouses (n=72). In addition, 11 FCHL patients were treated with atorvastatin to study the response in PCSK9 levels. PCSK9 levels were higher in FCHL patients compared with NL relatives and spouses: 96.1 compared with 78.7 and 82.0 ng/ml (P=0.004 and P=0.002 respectively). PCSK9 was significantly associated with both TAG (triacylglycerol) and apolipoprotein B levels (P<0.001). The latter relationship was accounted for by LDL (low-density lipoprotein)–apolipoprotein B (r=0.31, P=0.02), not by VLDL (very-low-density lipoprotein)–apolipoprotein B (r=0.09, P=0.49) in a subgroup of subjects (n=59). Heritability calculations for PCSK9 using SOLAR and FCOR software yielded estimates of 67–84% respectively (P<0.0001). PCSK9 increased from 122 to 150 ng/ml in 11 FCHL patients treated with atorvastatin (40 mg) once daily for 8 weeks (P=0.018). In conclusion, plasma PCSK9 is a heritable trait associated with both FCHL diagnostic hallmarks. These results, combined with the significant rise in PCSK9 levels after statin therapy, warrant further studies in order to unravel the exact role of PCSK9 in the pathogenesis and treatment of this highly prevalent genetic dyslipidaemia.

Inactivation of endothelial proprotein convertase 5/6 decreases collagen deposition in the cardiovascular system: role of fibroblast autophagy

2011 ◽  
Vol 89 (11) ◽  
pp. 1103-1111 ◽  
Author(s):  
Chiara Marchesi ◽  
Rachid Essalmani ◽  
Catherine A. Lemarié ◽  
Eyal Leibovitz ◽  
Talin Ebrahimian ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Collagen Deposition ◽  
Proprotein Convertase
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