scholarly journals Protective Effects of HBSP on Ischemia Reperfusion and Cyclosporine A Induced Renal Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Yuanyuan Wu ◽  
Junlin Zhang ◽  
Feng Liu ◽  
Cheng Yang ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Caspase 3 ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Protective Effects ◽  
Tubulointerstitial Damage ◽  
Apoptosis And Inflammation ◽  
The Right ◽  
Active Caspase

Ischemia reperfusion (IR) and cyclosporine A (CsA) injuries are unavoidable in kidney transplantation and are associated with allograft dysfunction. Herein, the effect and mechanism of a novel tissue protective peptide, helix B surface peptide (HBSP) derived from erythropoietin, were investigated in a rat model. The right kidney was subjected to 45 min ischemia, followed by left nephrectomy and 2-week reperfusion, with or without daily treatment of CsA 25 mg/kg and/or HBSP 8 nmol/kg. Blood urea nitrogen was increased by CsA but decreased by HBSP at 1 week and 2 weeks, while the same changes were revealed in urinary protein/creatinine only at 2 weeks. HBSP also significantly ameliorated tubulointerstitial damage and interstitial fibrosis, which were gradually increased by IR and CsA. In addition, apoptotic cells, infiltrated inflammatory cells, and active caspase-3+ cells were greatly reduced by HBSP in the both IR and IR + CsA groups. The 17 kD active caspase-3 protein was decreased by HBSP in the IR and IR + CsA kidneys, with decreased mRNA only in the IR + CsA kidneys. Taken together, it has been demonstrated, for the first time, that HBSP effectively improved renal function and tissue damage caused by IR and/or CsA, which might be through reducing caspase-3 activation and synthesis, apoptosis, and inflammation.

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

2020 ◽  
Author(s):  
Yuanyuan Wu ◽  
Weiwei Chen ◽  
Yufang Zhang ◽  
Aifen Liu ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Synergistic Effects ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Specific Treatment ◽  
Transcriptional Profile ◽  
Apoptosis And Inflammation ◽  
Active Caspase

Abstract Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation, (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-min renal bilateral ischemia and 48-h reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change > 1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6, SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

scholarly journals Overexpression of Ubiquinol-Cytochrome c Reductase Core Protein 1 May Protect H9c2 Cardiac Cells by Binding with Zinc

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tingting Yi ◽  
Xiaoxiao Wu ◽  
Zonghong Long ◽  
Guangyou Duan ◽  
Zhuoxi Wu ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Direct Evidence ◽  
Core Protein ◽  
Ischemia Reperfusion ◽  
Cardiac Cells ◽  
Protective Effects ◽  
Cytochrome C Reductase ◽  
Simulated Ischemia

In several recent studies, proteomics analyses suggest that increase of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is cardio-protective. However, direct evidence for this effect has not yet been obtained. Thus, the current study aimed to determine this effect and the mechanism underlying this effect. The results showed that overexpression of UQCRC1 protected H9c2 cardiac cells against in vitro simulated ischemia-reperfusion by maintaining mitochondrial membrane potential and suppressing the expression of caspase-3. These protective effects were significantly enhanced by exogenous Zn2+ but completely abolished by Zn2+-selective chelator TPEN. Furthermore, the upregulation of UQCRC1 reduced the concentration of free Zn2+ in mitochondria, whereas the downregulation of UQCRC1 increased the concentration of free Zn2+ in mitochondria. In conclusion, the overexpression of UQCRC1 can protect H9c2 cardiac cells against simulated ischemia/reperfusion, and this cardio-protective effect is likely mediated by zinc binding.

Paricalcitol pretreatment attenuates renal ischemia/reperfusion injury by inhibiting p38 MAPK and activating PI3K/Akt signaling pathways

2019 ◽  
Vol 44 (4) ◽  
pp. 452-461
Author(s):  
Zahide Cavdar ◽  
Cemre Ural ◽  
Ayse Kocak ◽  
Sevki Arslan ◽  
Sibel Ersan ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Albino Rats ◽  
Sod Activity ◽  
Interstitial Inflammation ◽  
Tnf Α ◽  
Active Caspase

Abstract Objective This study aimed to investigate the renoprotective effects of paricalcitol, a synhetic vitamin D analog, through its possible roles on p38 MAPK and PI3K/Akt signaling pathways to prevent oxidative stress, inflammation and apoptosis during renal I/R. Materials and methods Total 20 kidney tissues of sham (n = 6), subjected to renal I/R bilaterally for 45 min ischemia followed by 24 h reperfusion (n = 7) and paricalcitol (0.3 μg/kg, ip) pretreated Wistar albino rats (n =7) were used in this study. Interstitial inflammation and active caspase-3 expression were evaluated histologically. TNF-α, IL-1β, kidney injury molecule-1 (KIM-1), MDA and SOD activity in kidneys were analysed biochemically. Furthermore, activation of p38 MAPK, PI3K/Akt signaling pathways and NFκB p65 were evaluated by western blot. Results Paricalcitol pretreatment significantly reduced interstitial inflammation during renal I/R, which was consistent with decreased tumor TNF-α, IL-1β, active caspase-3 and KIM-1 expression. Paricalcitol also reduced MDA level and attenuated the reduction of SOD activity in the kidney during I/R. Moreover, paricalcitol could suppress the p38 MAPK and NFκB p65, and also activate PI3K/Akt signaling pathway during renal I/R. Conclusion All these findings indicate that paricalcitol may be an effective practical strategy to prevent renal I/R injury.

scholarly journals Vitamin C Inhibits Aggravated Eryptosis by Hydrogen Peroxide in Glucose-6-Phosphated Dehydrogenase Deficiency

2016 ◽  
Vol 39 (4) ◽  
pp. 1453-1462 ◽  
Author(s):  
Feng Shan ◽  
Rui Yang ◽  
Tiemei Ji ◽  
Fengjun Jiao
Keyword(s):  
Hydrogen Peroxide ◽  
Vitamin C ◽  
G6pd Deficiency ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Activity ◽  
Protective Effects ◽  
Blank Group ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Active Caspase

Background/Aims: The study was aimed to investigate if vitamin C could exert protective effects on development of eryptosis caused by glucose-6-phosphate dehydrogenase (G6PD) deficiency and hydrogen peroxide. Methods: Isolated erythrocytes with different G6PD activity (normal or deficient) were divided into various groups treated by either Vitamin C or H2O2. Phosphatidylserine (PS) extroversion rate was detected by Annexin V binding. The intracellular Ca2+ concentration was detected by Fluo3-fluorescence, and western blot was used to detect the expression of apoptosis factor caspase 3. Results: Compared with the blank group, the PS extroversion rate (P < 0.001), intracellular Ca2+ concentration (P < 0.001) and active caspase 3 expression level (P < 0.05) of erythrocytes significantly increased after treatment of 0.05% H2O2. Then the index of eryptosis significantly decreased after erythrocytes were treated with Vitamin C (1 mg/ml) for 30 min (all P < 0.05). The decline in erythrocytes with G6PD normal activity was more significant than those with G6PD deficiency. Conclusion: Vitamin C could effectively inhibit the eryptosis contributed by H2O2 oxidative stress, and the suppression on eryptosis with G6PD normal activity was more effective than that with G6PD deficiency.

Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade

2014 ◽  
Vol 307 (7) ◽  
pp. R879-R887 ◽  
Author(s):  
Naimeh Rafatian ◽  
Katherine V. Westcott ◽  
Roselyn A. White ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Time Course ◽  
Caspase 3 ◽  
Macrophage Infiltration ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Intracerebroventricular Infusion ◽  
Apoptosis And Inflammation ◽  
A Minor ◽  
The Brain ◽  
Active Caspase

After myocardial infarction (post-MI), inflammation and apoptosis contribute to progressive cardiac remodeling and dysfunction. Cardiac mineralocorticoid receptor (MR) and β-adrenergic signaling promote apoptosis and inflammation. Post-MI, MR activation in the brain contributes to sympathetic hyperactivity and an increase in cardiac aldosterone. In the present study, we assessed the time course of macrophage infiltration and apoptosis in the heart as detected by both terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and active caspase-3 immunostaining in both myocytes and nonmyocytes, as well as the effects of central MR blockade by intracerebroventricular infusion of eplerenone at 5 μg/day on peak changes in macrophage infiltration and apoptosis post-MI. Macrophage numbers were markedly increased in the infarct and peri-infarct zones and to a minor extent in the noninfarct part of the left ventricle at 10 days post-MI and decreased over the 3-mo study period. Apoptosis of both myocytes and nonmyocytes was clearly apparent in the infarct and peri-infarct areas at 10 days post-MI. For TUNEL, the increases persisted at 4 and 12 wk, but the number of active caspase-3-positive cells markedly decreased. Central MR blockade significantly decreased CD80-positive proinflammatory M1 macrophages and increased CD163-positive anti-inflammatory M2 macrophages in the infarct. Central MR blockade also reduced apoptosis of myocytes by 40–50% in the peri-infarct and to a lesser extent of nonmyocytes in the peri-infarct and infarct zones. These findings indicate that MR activation in the brain enhances apoptosis both in myocytes and nonmyocytes in the peri-infarct and infarct area post-MI and contributes to the inflammatory response.

scholarly journals Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yufang Zhang ◽  
Yuanyuan Wu ◽  
Wei Wang ◽  
Feng Liu ◽  
Yiwen Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cyclosporine A ◽  
Ischemia Reperfusion ◽  
Urinary Albumin ◽  
Tubulointerstitial Damage ◽  
Kidney Epithelial Cells ◽  
Underlying Mechanisms ◽  
Gsk 3Β ◽  
Induced Apoptosis ◽  
Interfering Rna

Renal ischemia–reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.

scholarly journals Galuteolin suppresses proliferation and inflammation in TNF-α-induced RA-FLS cells by activating HMOX1 to regulate IKKβ/NF-κB pathway

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yin Guan ◽  
Xiaoqian Zhao ◽  
Weiwei Liu ◽  
Yue Wang
Keyword(s):  
Cell Proliferation ◽  
Caspase 3 ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tnf Α ◽  
Apoptosis And Inflammation ◽  
Dose Dependent ◽  
Anti Inflammation

Abstract Objective Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation. Methods After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expressions of Iκκβ, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MMP-1 were determined by ELISA. Results Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promotes cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3, and Bax, while reducing the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκβ, p-p65, and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1β, IL-6, IL-8, and MMP-1 in RA-FLS cells. Conclusion Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.

scholarly journals Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Qunwen Pan ◽  
Yan Wang ◽  
Qing Lan ◽  
Weiquan Wu ◽  
Zhenxuan Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Pi3k Inhibitor Ly294002 ◽  
Cell Functions ◽  
Hypoxia Reoxygenation

Mesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-126 is an important regulator of EC functions and angiogenesis. In this study, we determined whether EXs released from MSC-EXs provided beneficial effects on hypoxia/reoxygenation- (H/R-) injured ECs by transferring miR-126. MSCs were transfected with a miR-126 mimic or miR-126 short hairpin RNA to obtain miR-126-overexpressing MSC-EXs (MSC-EXsmiR-126) and miR-126 knockdown MSC-EXs (MSC-EXsSimiR-126). For functional studies, H/R-injured ECs were coincubated with various MSC-EXs. The viability, migration, tube formation ability, and apoptosis of ECs were measured. miR-126 and proangiogenic/growth factor (VEGF, EGF, PDGF, and bFGF) expressions were detected by qRT-PCR. Akt, p-Akt, p-eNOS, and cleaved caspase-3 expressions were examined by western blot. The PI3K inhibitor (LY294002) was used in pathway analysis. We found that overexpression/knockdown of miR-126 increased/decreased the proliferation of MSCs, as well as miR-126 expression in their derived MSC-EXs. MSC-EXsmiR-126 were more effective in promoting proliferation, migration, and tube formation ability of H/R-injured ECs than MSC-EXs. These effects were associated with the increase in p-Akt/Akt and p-eNOS, which could be abolished by LY294002. Besides, MSC-EXsmiR-126 were more effective than MSC-EXs in reducing the apoptosis of ECs, coupled with the decrease in cleaved caspase-3. Moreover, compared to MSC-EXs, MSC-EXsmiR-126 significantly upregulated the level of VEGF, EGF, PDGF, and bFGF in H/R-injured ECs. Downregulation of miR-126 in MSC-EXs inhibited these effects of MSC-EXs. The results suggest that MSC-EXs could enhance the survival and angiogenic function of H/R-injured ECs via delivering miR-126 to ECs and subsequently activate the PI3K/Akt/eNOS pathway, decrease cleaved caspase-3 expression, and increase angiogenic and growth factors.

scholarly journals Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats

2009 ◽  
Vol 297 (2) ◽  
pp. F362-F370 ◽  
Author(s):  
Dae Eun Choi ◽  
Jin Young Jeong ◽  
Beom Jin Lim ◽  
Sarah Chung ◽  
Yoon Kyung Chang ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Renal Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Erk Phosphorylation ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide ◽  
Structural Levels

Sildenafil was the first selective inhibitor of phosphodiesterase-5 (PDE5) to be widely used for treating erectile dysfunction. Many recent studies have investigated the cardioprotective role of sildenafil in animal models. We evaluated the protective effects of sildenafil in experimental renal ischemia-reperfusion (IR) injury in two studies. In study 1, male Sprague-Dawley rats were divided into four groups: sham, sildenafil-treated sham, vehicle-treated IR, and sildenafil-treated IR groups. In study 2, we divided the rats into two groups: sildenafil-treated IR rats and PD98059 (ERK inhibitor)+sildenafil-treated IR rats. Functional parameters of the kidney were evaluated at the molecular and structural levels. Blood urea nitrogen (BUN) and serum creatinine levels were lower in sildenafil-treated IR rats than in vehicle-treated IR rats. The expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) proteins in sildenafil-treated IR rats was significantly higher than in vehicle-treated IR rats. Pretreatment with sildenafil in IR rats increased ERK phosphorylation and reduced the renal Bax/Bcl-2 ratio, renal caspase-3 activity, and terminal dUTP nick end-labeling-positive apoptotic cells. In contrast, PD98059 treatment increased BUN and serum creatinine levels and attenuated the sildenafil-induced expression of pERK, iNOS, eNOS, and Bcl-2. PD98059 also increased caspase-3 activity but did not decrease the sildenafil-induced accumulation of cGMP. In conclusion, this study suggests that sildenafil has antiapoptotic effects in experimental IR renal injury via ERK phosphorylation, induction of iNOS and eNOS production, and a decrease in the Bax/Bcl-2 ratio.

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