scholarly journals Dose-dependent protective effect of propofol against mitochondrial dysfunction in ischaemic/reperfused rat heart: role of cardiolipin

2008 ◽  
Vol 153 (8) ◽  
pp. 1641-1649 ◽  
Author(s):  
H Shao ◽  
J Li ◽  
Y Zhou ◽  
Z Ge ◽  
J Fan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Mitochondrial Dysfunction ◽  
Rat Heart ◽  
Dose Dependent

Zymogen Protein C as a Novel Modulator of Cancer Progression In Murine Models

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 718-718
Author(s):  
Geerte L. Van Sluis ◽  
Paris Margaritis ◽  
Michael Sliozberg ◽  
Jenna Mauer ◽  
Armida Faella ◽  
...  
Keyword(s):  
Protective Effect ◽  
Tumor Progression ◽  
Lung Metastasis ◽  
Protein C ◽  
Tumor Metastasis ◽  
Minimal Risk ◽  
Dependent Manner ◽  
Molecular Therapeutics ◽  
Dose Dependent

Abstract Abstract 718 Recent evidence on the role of the protein C (PC) pathway in tumor progression of the experimental mouse melanoma model has revealed that inhibition of the cytoprotective effects of endogenous activated PC (aPC) enhances tumor cell extravasation, whereas exogenous administration of recombinant human APC has a protective effect. Moreover transgenic mice overexpressing endothelial PC receptor (EPCR) in tissue endothelium exhibit low rates of tumor metastasis. Here we report our findings in C57Bl/6 mice expressing murine forms of APC or zymogen PC by viral-mediated gene transfer. Vector-injected mice resulted in continuous expression of murine APC (mAPC) or PC (mPC), which reached plateau levels after week 2. On week 3, we administered B16F10 murine melanoma cells (3.5×10^5) intravascularly and analyzed the rates of lung metastasis 21 days later compared to age and gender matched saline-injected groups (control cohort=26 mice). We observed a dose-dependent protective effect of mAPC. Mice expressing mAPC at levels of 7.3 ± 1.5 ng/ml (n=8) or lower (determined by a functional ELISA-capture assay) did not differ from saline injected mice (that had baseline mAPC levels < 3 ng/ml). By increasing the vector dose, mAPC levels of 25.6 ± 4.8 ng/ml (n=16) to 118 ±6 ng/ml (n=10) reduced the numbers of lung metastasis compared to saline injected mice (p<0.05). To investigate the contribution of the cytoprotective/anticoagulant role of mAPC, we injected mice with a variant form of mAPC with reduced anticoagulant but intact cytoprotective activity (mAPC-5A). Following melanoma cell infusion, animals expressing levels of mAPC-5A ranging from 15.2 ± 3.2 ng/ml (n=16) to 80.4 ± 4.7 ng/ml (n=10) exhibited rates of lung metastasis similar to controls. To further explore the anticoagulant pathway in this metastasis model, we injected mice with AAV expressing zymogen mPC. There was a dose-dependent increase in the mPC levels measured by a chromogenic assay resulting in 3–4 fold of normal levels. However, this was not associated with increased levels of mAPC compared to saline-injected mice. Notably, in the mPC expressing mice (n=26), the rates of tumor metastasis were significantly reduced compared to controls (p<0.005). The protective effect of zymogen mPC remained even in the absence of protease-activated receptor (PAR-1), one main cellular receptor for the APC-mediated cytoprotective effect. In particular, the lung metastasis rates in PAR-1 null mice expressing mPC (n=21) were lower than PAR-1 null mice injected with saline (n=15) (p<0.01). Lastly, the hemostatic effects of the expressed transgenes (mPC, mAPC and mAPC-5A) in all mice were investigated. Prolongation of the activated partial prothrombin time and increase blood loss following tail clipping assay was restricted to animals expressing APC-WT in a dose-dependent manner but not in APC-5A or zymogen PC compared to controls. These findings support a novel and important role of zymogen PC in modulating tumor progression with minimal risk of bleeding. Disclosures: High: Genzyme, Inc: Consultancy, Patents & Royalties; Third Rock Ventures: Consultancy; PTC Therapeutics:; Amsterdam Molecular Therapeutics:; Sangamo Biosciences:; Novo-Nordisk: Consultancy; Shire, Inc.: Consultancy.

scholarly journals Triggering role of nitric oxide in the delayed protective effect of monophosphoryl lipid A in rat heart

1999 ◽  
Vol 127 (8) ◽  
pp. 1892-1898 ◽  
Author(s):  
Katalin György ◽  
Bernard Muller ◽  
Agnes Végh ◽  
Andrei L Kleschyov ◽  
Jean-Claud Stoclet
Keyword(s):  
Nitric Oxide ◽  
Protective Effect ◽  
Rat Heart ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemiareperfusion: role of cardiolipin

2006 ◽  
Vol 20 (2) ◽  
pp. 269-276 ◽  
Author(s):  
G. Petrosillo ◽  
N. Di Venosa ◽  
M. Pistolese ◽  
G. Casanova ◽  
E. Tiravanti ◽  
...  
Keyword(s):  
Protective Effect ◽  
Mitochondrial Dysfunction

scholarly journals The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Yejun Yan ◽  
Hongwei Dang ◽  
Xin Zhang ◽  
Xia Wang ◽  
Xiaodong Liu
Keyword(s):  
Protective Effect ◽  
Rat Heart ◽  
Myocardial Infarct ◽  
Tyrosine Phosphatase ◽  
Protective Role ◽  
Myocardial Infarct Size ◽  
Loss Of Function

Abstract MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.

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