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The Role Of Calpain-2 In Exercise Improvement Of Liver Endoplasmic Reticulum Stress And Related Mechanisms

Posted on:2018-03-11Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:2354330515477055Subject:Human Movement Science
Abstract/Summary:PDF Full Text Request
Endoplasmic reticulum stress refers to pathological and physiological proce dure which caused by various reasons.ERS disturb the function of endoplasmic reticulum and affect the synthesis of proteins.Liver,as a significant part of metabolic system in human body,liver ERS may induce a series of metabolic diseases,such as obesity,hypertension,hyperlipidemia,diabetes et al.ERS existed in liver have became major risk factor of main diseases and thus become a threat to human’ health.Calpain-2 is a isoform of calcium-activated neutralprotease,the recent study showed that the activation of Calpain-2 in human body may associate with the pathogenesis of some diseases,such as liver ERS.However,the effect and mechanism of Calpain-2 on liver ERS is still unknown.Objectives:This study established liver ERS model after feeding rats with high fat diet for 8 weeks,and treated high fat diet rats with swimming for 8 weeks.After taking materials,analyzed calpain-2 and other indicators,to explore effect and mechanism research on calpain-2 in exercising alleviated liver ERS,and further provided theoretical evidence for exercise alleviated some diseases.Methods:30 male Sprague-Dawley rats were randomly divided into control group(C,n=10),high fat diet ERS model group(HF,n=10),high fat diet ERS model and swimming exercise group(HE,n=10).Rats in C group were fed with normal food(13% fat),rats in HF group were fed with high fat diet(45% fat),rats in HE group were fed with high fat diet meanwhile exerted with swimming for 8 weeks.After 8 weeks took materials from C,HF,HE group rats.Serum free fatty acids were measured by enzymatic colorimetric assay;the protein expression of Calpain-2 and Atg7 in liver was detected by Western Blotting;mRNA expression of Calpain-2,Atg7,Grp78,Chop and EIF2α in liver was evaluated by RT-qPCR.Results:(1)Compared with C group,the mRNA expression of Grp78,Chop and EIF2α in liver of HF group increased significantly(p<0.01).The results showed that the ERS model was established successfully through high fat diet.(2)Compared with C group,the concentration of serum FFAs in HF group increased significantly(p<0.01);the RT-qPCR’ results and the western blotting results showed that compared with C group,the mRNA and protein expression of liver Calpain-2 in HF group up-regulated significantly,while the mRNA and protein expression of liver Atg7 in HF group down-regulated significantly(p<0.01).These results suggested that high fat diet could up-regulate Calpain-2 and inhibit Atg7 in liver,thus induced markers of ERS: Grp78,Chop and EIF2α.(3)Compared with HF group,the concentration of serum FFAs in HE group decreased significantly(p<0.01);the RT-qPCR’ results and the western blotting results showed that compared with HF group,the mRNA and protein expression of liver Calpain-2 in HE group down-regulated significantly,while the mRNA and protein expression of liver Atg7 in HE group up-regulated significantly(p<0.01).Compared with HF group,the mRNA expression of Grp78,Chop and EIF2α in liver of HE group decreased significantly(p<0.01).These results showed that exercise could effectively alleviate liver ERS.Conclusions:(1)After 8 weeks high fat dietary,the liver ERS model in rats established successfully.(2)Exercise could effectively alleviate liver ERS.Calpain-2 plays a crucial role in exercise alleviating liver ERS.The potential mechanism of Calpain-2 in inducing liver ERS: high fat diet increased FFAs in serum,serum FFAs transported to liver and upregulated mRNA and protein expression of liver Calpain-2,thus inhibited Atg7’s expression in liver.The inhibition of Atg7 could induce ERS marker Grp78,Chop and EIF2α,suggested that ERS happened in liver.
Keywords/Search Tags:endoplasmic reticulum stress, Calpain-2, high fat diet, Grp78, Chop, Atg7, Exercise
PDF Full Text Request
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