1.Effect of activated PAR-1 on the expression of CXCR4 mRNA,proliferation and migration of mouse endothelial progenitor cells
Jinglan DAI ; Bo PAN ; Ping GU ; Haigang MU ; Jiasi BAI
Chongqing Medicine 2013;(33):4056-4058,4061
Objective To explore the effect of protease-activated receptor 1(PAR-1) activation on the expression of CXCR4 mR-NA of mouse endothelial progenitor cells (EPCs) and proliferation ,migration of EPCs .Methods Mouse EPCs were activated by different concentration of SFLLRN (one agonist of PAR-1) ,or transfected by small interfering RNA of PAR-1 .The expressions of PAR-1 and CXCR4 mRNA of EPCs were detected by fluorescent quantitative real-time PCR .Proliferation ,migration of EPCs were detected by MTT ,Transwell chambers respectively .Results The expressions of PAR-1 and CXCR4 mRNA in SFLLRN group were higher than that in other groups(P< 0 .05) .The expression of CXCR4 mRNA was highly positive correlation with PAR-1 mRNA(r=0 .991) .The proliferation ,migration of mouse EPCs were induced by activation of PAR-1 .Conclusion Activation of PAR-1 promotes cell proliferation and migration of mouse EPCs ,this effect may be depended on CXCR4 .
2.The influence of hyponatremia on prognosis in hospitalized patients with chronic heart failure
Bo PAN ; Min JIA ; Haigang MU ; Chengming YANG ; Ping GU
Chongqing Medicine 2013;(30):3610-3611,3614
Objective To study the influence of hyponatremia on prognosis in hospitalized patients with chronic heart failure . Methods A total of 322 patients with chronic heart failure from Feb .2006 to Aug .2012 were retrospectively reviewed and random-ly divided into hyponatremia group(n=161) and normal serum sodium group(n=161) .The clinical data of the two groups were compared .Results There were significant difference between the two groups in the BNP levels ,length of stay ,hospital mortality and readmission rates(P<0 .05) .Serum sodium concentration in hyponatremia group was decreased with the decrease of cardiac function(P<0 .05) ,BNP levels was elevated with the decrease of blood sodium level (P<0 .05) ,days of hospitalization and hospital mortality were increased with the decrease of cardiac function (P< 0 .05) .Conclusion Patients with heart failure combined hy-ponatremia have poor cardiac function ,higher in-hospital mortality and readmission rates and longer hospital stay .
3.Poly-PR in C9ORF72-Related Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Causes Neurotoxicity by Clathrin-Dependent Endocytosis.
Rui WANG ; Xingyun XU ; Zongbing HAO ; Shun ZHANG ; Dan WU ; Hongyang SUN ; Chenchen MU ; Haigang REN ; Guanghui WANG
Neuroscience Bulletin 2019;35(5):889-900
GGGGCC repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9ORF72 produce five dipeptide repeat (DPR) proteins by an unconventional repeat-associated non-ATG (RAN) translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs (poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase (JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PR-induced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependent endocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.