scholarly journals Knockdown of miR-384-3p Protects Against Myocardial Ischemia-Reperfusion Injury in Rats Through Targeting HSP70

2021 ◽  
Vol 24 (1) ◽  
pp. E143-E150
Author(s):  
Chusheng Huang ◽  
Hailong Deng ◽  
Wen Zhao ◽  
Lei Xian
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Present Report ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Triphenyltetrazolium Chloride ◽  
Dynamic Expression ◽  
Myocardial Ischemia Reperfusion ◽  
High Degree

Background: Myocardial infarction (MI) and heart failure remain critical states of heart disease with high mortality. Previous studies have indicated that miRNA has cardioprotective effects and can resist myocardial ischemia–reperfusion (I/R) injury. However, the role of mir-384-3p in MI has not been reported, and whether this miRNA can regulate the apoptosis of cardiomyocytes needs to be verified. Methods: The effect of hypoxia–reperfusion (H/R) on cardiomyocyte activity was detected using MTT assay. MiR-384-3p was knocked down or overexpressed in cardiomyocytes H/R models by pretreatment with miR-384-3p mimic or inhibitor to verify the function of miR-384-3p in H/R. Circulating levels of miR-384-3p was detected by quantitative realtime PCR, and protein expression was detected by western blotting. TUNEL staining and flow cytometry demonstrated a high degree of myocardium apoptosis after H/R induction. Dual-Luciferase Reporter Assay detected dynamic expression of miR-384-3p and HSP70. The infarction size of I/R rats was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Results: MiR-384-3p was closely related to cardiomyocyte activity in H/R progression. Increased expression of mir-384-3p can promote the production of cleaved caspase-3 and cleaved PARP, thereby regulating cardiomyocyte apoptosis. HSP70 was a target of miR-384-3p and HSP70 silencing aggravated H/R-induced cardiomyocyte dysfunction. In an animal model, the expression level of HSP70 is regulated by miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats. Conclusion: In conclusion, the present report identified that HSP70 was a potential target of miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats. Therefore, this study provides a novel therapeutic approach for the treatment of MI from bench to clinic.

scholarly journals Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1

2020 ◽  
Author(s):  
Jianfeng Chen ◽  
Mingming Zhang ◽  
Shouyan Zhang ◽  
Junlong Wu ◽  
Shufeng Xue
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sirtuin 1 ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Cells ◽  
Myocardial Ischemia Reperfusion

Abstract Background: This study aimed to investigate the regulatory effect of rno-microRNA-30c-5p (rno-miR-30c-5p) on myocardial ischemia reperfusion (IR) injury in rats and the underlying molecular mechanisms.Methods: A rat model of myocardial IR injury was established. The infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. The pathologic changes of myocardial tissues were detected by hematoxylin-eosin staining. The apoptosis of myocardial cells was measured by TUNEL staining and flow cytometry. The mRNA expression of rno-miR-30c-5p and Sirtuin 1 (SIRT1) was detected by quantitative real-time PCR. The levels of IL-1β, IL-6 and TNF-α were detected by enzyme linked immunosorbent assay. The protein expression of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 was detected by Western blot. The interaction between rno-miR-30c-5p and SIRT1 was predicted by TargetScan, and further identified by dual luciferase reporter gene and RNA immunoprecipitation assay.Results: The myocardial IR injury model was successfully established in rats. IR induced the myocardial injury in rats and increased the expression of rno-miR-30c-5p. Overexpression of rno-miR-30c-5p enhanced the inflammation, promoted the apoptosis, and activated NF-κB pathway in IR myocardial cells. SIRT1 was the target gene of rno-miR-30c-5p. Silencing of SIRT1 reversed the effects of rno-miR-30c-5p inhibitor on the apoptosis and NF-κB pathway in IR myocardial cells.Conclusions: Rno-miR-30c-5p promoted the myocardial IR injury in rats through activating NF-κB pathway and down-regulating SIRT1.

scholarly journals Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1.

2020 ◽  
Author(s):  
Jianfeng Chen ◽  
Mingming Zhang ◽  
Shouyan Zhang ◽  
Junlong Wu ◽  
Shufeng Xue
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sirtuin 1 ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Cells ◽  
Myocardial Ischemia Reperfusion

Abstract Background: This study aimed to investigate the regulatory effect of rno-microRNA-30c-5p (rno-miR-30c-5p) on myocardial ischemia reperfusion (IR) injury in rats and the underlying molecular mechanisms.Methods: A rat model of myocardial IR injury was established. The infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. The pathologic changes of myocardial tissues were detected by hematoxylin-eosin staining. The apoptosis of myocardial cells was measured by TUNEL staining and flow cytometry. The mRNA expression of rno-miR-30c-5p and Sirtuin 1 (SIRT1) was detected by quantitative real-time PCR. The levels of IL-1β, IL-6 and TNF-α were detected by enzyme linked immunosorbent assay. The protein expression of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 was detected by Western blot. The interaction between rno-miR-30c-5p and SIRT1 was predicted by TargetScan, and further identified by dual luciferase reporter gene and RNA immunoprecipitation assay.Results: The myocardial IR injury model was successfully established in rats. IR induced the myocardial injury in rats and increased the expression of rno-miR-30c-5p. Overexpression of rno-miR-30c-5p enhanced the inflammation, promoted the apoptosis, and activated NF-κB pathway in IR myocardial cells. SIRT1 was the target gene of rno-miR-30c-5p. Silencing of SIRT1 reversed the effects of rno-miR-30c-5p inhibitor on the apoptosis and NF-κB pathway in IR myocardial cells.Conclusions: Rno-miR-30c-5p promoted the myocardial IR injury in rats through activating NF-κB pathway and down-regulating SIRT1.

scholarly journals Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1

2020 ◽  
Author(s):  
Jianfeng Chen ◽  
Mingming Zhang ◽  
Shouyan Zhang ◽  
Junlong Wu ◽  
Shufeng Xue
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sirtuin 1 ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Cells ◽  
Myocardial Ischemia Reperfusion

Abstract Background: This study aimed to investigate the regulatory effect of rno-microRNA-30c-5p (rno-miR-30c-5p) on myocardial ischemia reperfusion (IR) injury in rats and the underlying molecular mechanisms. Methods: A rat model of myocardial IR injury was established. The infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. The pathologic changes of myocardial tissues were detected by hematoxylin-eosin staining. The apoptosis of myocardial cells was measured by TUNEL staining and flow cytometry. The mRNA expression of rno-miR-30c-5p and Sirtuin 1 (SIRT1) was detected by quantitative real-time PCR. The levels of IL-1β, IL-6 and TNF-α were detected by enzyme linked immunosorbent assay. The protein expression of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 was detected by Western blot. The interaction between rno-miR-30c-5p and SIRT1 was predicted by TargetScan, and further identified by dual luciferase reporter gene and RNA immunoprecipitation assay. Results: The myocardial IR injury model was successfully established in rats. IR induced the myocardial injury in rats and increased the expression of rno-miR-30c-5p. Overexpression of rno-miR-30c-5p enhanced the inflammation, promoted the apoptosis, and activated NF-κB pathway in IR myocardial cells. SIRT1 was the target gene of rno-miR-30c-5p. Silencing of SIRT1 reversed the effects of rno-miR-30c-5p inhibitor on the apoptosis and NF-κB pathway in IR myocardial cells. Conclusions: Rno-miR-30c-5p promoted the myocardial IR injury in rats through activating NF-κB pathway and down-regulating SIRT1.

scholarly journals Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1

2020 ◽  
Author(s):  
Jianfeng Chen ◽  
Mingming Zhang ◽  
Shouyan Zhang ◽  
Junlong Wu ◽  
Shufeng Xue
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sirtuin 1 ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Cells ◽  
Myocardial Ischemia Reperfusion

Abstract Background: This study aimed to investigate the regulatory effect of rno-microRNA-30c-5p (rno-miR-30c-5p) on myocardial ischemia reperfusion (IR) injury in rats and the underlying molecular mechanisms. Methods: A rat model of myocardial IR injury was established. The infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. The pathologic changes of myocardial tissues were detected by hematoxylin-eosin staining. The apoptosis of myocardial cells was measured by TUNEL staining and flow cytometry. The mRNA expression of rno-miR-30c-5p and Sirtuin 1 (SIRT1) was detected by quantitative real-time PCR. The levels of IL-1β, IL-6 and TNF-α were detected by enzyme linked immunosorbent assay. The protein expression of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 was detected by Western blot. The interaction between rno-miR-30c-5p and SIRT1 was predicted by TargetScan, and further identified by dual luciferase reporter gene and RNA immunoprecipitation assay. Results: The myocardial IR injury model was successfully established in rats. IR induced the myocardial injury in rats and increased the expression of rno-miR-30c-5p. Overexpression of rno-miR-30c-5p enhanced the inflammation, promoted the apoptosis, and activated NF-κB pathway in IR myocardial cells. SIRT1 was the target gene of rno-miR-30c-5p. Silencing of SIRT1 reversed the effects of rno-miR-30c-5p inhibitor on the apoptosis and NF-κB pathway in IR myocardial cells. Conclusions: Rno-miR-30c-5p promoted the myocardial IR injury in rats through activating NF-κB pathway and down-regulating SIRT1.

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

scholarly journals The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1365-1375 ◽  
Author(s):  
Jie Jian ◽  
Feifei Xuan ◽  
Feizhang Qin ◽  
Renbin Huang
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. Methods: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-κBp65, Bcl-2 and Bax were detected by western blotting. Results: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-κBp65 and Bax, but enhanced the expression of Bcl-2. Conclusion: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis.

scholarly journals Visnagin ameliorates myocardial ischemia/reperfusion injury through the promotion of autophagy and the inhibition of apoptosis

2020 ◽  
Vol 64 (s2) ◽  
Author(s):  
Hai-rong Fu ◽  
Xiao-shan Li ◽  
Yong-hui Zhang ◽  
Bin-bin Feng ◽  
Lian-hong Pan
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Sham Group ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tunel Staining ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Visnagin is a furanochromone and one of the main compounds of Ammi visnaga L. that had been used to treat nephrolithiasis in Ancient Egypt. Nowadays, visnagin was widely used to treat angina pectoris, urolithiasis and hypertriglyceridemia. The potential mechanisms of visnagin involved in inflammation and cardiovascular disease were also identified. But the protective effect of visnagin on myocardial ischemia/reperfusion injury has not been confirmed. Our aim was, for the first time, to investigate the potential protective effect of visnagin on cardiac function after myocardial ischemia-reperfusion injury in a rat model, and to identify its underlying mechanism involving the inhibition of apoptosis and induction of autophagy. Thirty SD rats were randomly divided into sham group, ischemia/reperfusion group (IR), ischemia/reperfusion with visnagin (IR + visnagin) group. Myocardial ischemia/Reperfusion injury model was established. Hemodynamic measurements and echocardiography were used to analyze cardiac function, TUNEL staining and caspase activity, LC3 dots were detected with immunofluorescence staining, LC3 expression was evaluated by western blot analysis, transmission electron microscopy (TEM) was used to detect autophagosomes. Compared with the sham group and visnagin group, the cardiac dysfunction, LC3II, autophagy flow in the IR+ visnagin group increased significantly (P<0.01), but the activity of caspase-3 and caspase-9 and the apoptotic in the IR + visnagin group decreased significantly (P<0.01). In conclusion, visnagin may play a protective role in ischemia/reperfusion injury by inducing autophagy and reducing apoptosis.

Mechanisms of Paeoniflorin against myocardial ischemia reperfusion injury based on network pharmacology

2021 ◽  
Vol 11 (9) ◽  
pp. 1505-1515
Author(s):  
Chengguo Zhao ◽  
Meifang Yin ◽  
Feng Li ◽  
Wenpei Ling ◽  
Chunyu Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Myocardial Enzymes

Ischemic heart disease (IHD) is the primary reason of death of cardiovascular diseases. Paeoniflorin (PF), a monoterpene glycoside extracted from Radix Paeoniae Rubra or Paeoniae Radix Alba, can ameliorate myocardial ischemia/reperfusion injury (MIRI), but its mechanism is not still defined. In this study, network pharmacology was utilized, the protein interaction network between PF and MIRI targets were screened for bioenrichment analysis. Moreover, the anti-MIRI effects of PF (30, 60 and 120 mg/kg) were investigated in vivo on rats for verification. The myocardial infarction area was assessed by TTC/Evans blue staining and morphological changes of tissues were evaluated using hematoxylin and eosin staining. The contents of myocardial enzymes and oxidation resistance were measured. The cell apoptosis was evaluated using TUNEL staining and the expression of proteins was estimated using Western Blot. In the results, the relevant targets and the biological processes of PF against MIRI were screened out, indicating its anti-MIRI potential pharmacological effects of PF. 120 mg/kg PF can shrink infarction area after ischemia/reperfusion, ameliorate pathological morphology in myocardial tissue, lower the levels of myocardial enzymes, and attenuate oxidative stress. Furthermore, PF could reduce the positive rate of TUNEL staining caused by MIRI. Moreover, 120 mg/kg PF could depress the protein levels of Bax, Caspase-3, Beclin-1 and Cathepsin B and increase the protein level of Bcl-2 on rats after reperfusion. In conclusion, Paeoniflorin has an anti-MIRI effect in rats via coordinate regulation of anti-oxidative stress, anti-apoptosis and inhibition of autophagy.

scholarly journals The Guizhi Gancao Decoction Attenuates Myocardial Ischemia-Reperfusion Injury by Suppressing Inflammation and Cardiomyocyte Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yuan Gao ◽  
Ge Song ◽  
Ying-Jie Cao ◽  
Kui-Po Yan ◽  
Bin Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Cardiomyocyte Apoptosis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Triphenyltetrazolium Chloride ◽  
Traditional Chinese Herbal Medicine ◽  
Myocardial Ischemia Reperfusion

Guizhi Gancao Decoction (GGD) is a well-known traditional Chinese herbal medicine for the treatment of various cardiovascular diseases, such as myocardial ischemia-reperfusion (I/R) injury and arrhythmia. However, the mechanism by which GGD contributes to the amelioration of cardiac injury remains unclear. The aim of this study was to investigate the potential protective role of GGD against myocardial I/R injury and its possible mechanism. Consistent with the effect of the positive drug (Trimetazidine, TMZ), we subsequently validated that GGD could ameliorate myocardial I/R injury as evidenced by histopathological examination and triphenyltetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated that GGD suppressed myocardial apoptosis, which may be related to the upregulation of Bcl-2, PPARα, and PPARγ and downregulation of Bax, caspase-3, and caspase-9. Pretreatment with GGD attenuated the levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and IL-1β in serum by inhibiting Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. These results indicated that GGD exhibits cardioprotective effects on myocardial I/R injury through inhibition of the TLR4/NF-κB signaling pathway, which led to reduced inflammatory response and the subsequent cardiomyocyte apoptosis.

Abstract 13: Nur77 Translocation from Nucleus to Mitochondria Contributes to the Enhanced Susceptibility to Ischemia-Reperfusion Injury in Diabetic Hearts

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Jingyi Liu ◽  
Peilin Liu ◽  
Min Jia ◽  
Haifeng Zhang ◽  
Chao Gao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Orphan Receptor ◽  
Tunel Staining ◽  
Cytochrome C Release ◽  
Expression Levels ◽  
Myocardial Ischemia Reperfusion ◽  
Interfering Rna

Diabetes is associated with increased prevalence of ischemic heart disease which accounts for the high incidence of death in the diabetic population. In response to various pro-apoptotic treatments, Nur77, a nuclear orphan receptor, translocates from the nucleus to mitochondria where it induces cytochrome c release and apoptosis in cancer cells. However, the role of Nur77 in diabetic myocardial ischemia/reperfusion (MI/R) injury remains elusive. Ten-week-old male C57BL/6J mice (WT) and ob/ob mice (OB) were subjected to 30 min of ischemia and 3 or 24 hrs of reperfusion. Compared with WT, the OB hearts exhibited more severe MI/R injury as evidenced by more ROS production, increased infarct size, caspase-3 activity, TUNEL staining and decreased cardiac function (n=8, all P <0.05). There was no significantly difference in total Nur77 expression levels between sham and MI/R group in WT mice. However, MI/R caused significant Nur77 mitochondria translocation as evidenced by decreased nuclear and increased cytosolic/mitochondrial Nur77 levels (all P <0.01). Comparing to WT, total Nur77 expression levels were significantly reduced in OB heart before MI/R ( P <0.01 vs. WT). However, MI/R caused more significant Nur77 mitochondrial translocation in OB mice, reaching a level that was not different from that seen in WT after MI/R ( P >0.01 vs. WT). Intramyocardial small-interfering RNA (Nur77-siRNA) injection specifically knocked-down the myocardial Nur77, increased ejection fraction and reduced infarct size/apoptosis after MI/R in both WT and OB mice (all P <0.05). However, more significant cardioprotection of Nur77 knockdown was observed in OB mice than that seen in WT. Collectively, we demonstrated firstly that the increased translocation of Nur77 from nucleus to mitochondria partly contributes to the enhanced susceptibility to MI/R in diabetic hearts. Interventions blocking this subcellular redistribution of Nur77 may be a potential therapy for the treatment of diabetic heart injury. Key Words: Nur77 • Mitochondria Translocation • Myocardial ischemia/reperfusion • Diabetes

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