scholarly journals Upregulation of UCP2 Expression Protects against LPS-Induced Oxidative Stress and Apoptosis in Cardiomyocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jinda Huang ◽  
Wanwan Peng ◽  
Yijun Zheng ◽  
Hu Hao ◽  
Sitao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Protein Level ◽  
Caspase 3 ◽  
Uncoupling Protein ◽  
Dependent Manner ◽  
Mitochondrial Cytochrome ◽  
Protein Levels ◽  
Ucp2 Expression ◽  
Mitochondrial Cytochrome C

Uncoupling protein 2 (UCP2) has a cardioprotective role under septic conditions, but the underlying mechanism remains unclear. This study aimed at investigating the effects of UCP2 on the oxidative stress and apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS). First, LPS increased UCP2 expression in cardiomyocytes in a time-dependent manner. LPS increased the production of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and malondialdehyde (MDA) and decreased the level of superoxide dismutase (SOD). However, UCP2 knockdown increased the LPS-induced cardiac injury and oxidative stress. In addition, LPS damaged the mitochondrial ultrastructure and led to the disruption of mitochondrial membrane potential (MMP), as well as the release of mitochondrial cytochrome c. UCP2 knockdown aggravated mitochondrial injury and the release of mitochondrial cytochrome c. LPS increased the protein levels of Bax and cleaved-caspase-3, decreased the protein level of Bcl-2, and upregulated the protein level of mitogen-activated protein kinase. However, upon UCP2 knockdown, the protein levels of Bax and cleaved-caspase-3 increased even further, and the protein level of Bcl-2 was further decreased. The protein level of phosphorylated p38 was also further enhanced. Thus, UCP2 protects against LPS-induced oxidative stress and apoptosis in cardiomyocytes.

Platycodon grandiflorum Induces Apoptosis in SKOV3 Human Ovarian Cancer Cells Through Mitochondrial-Dependent Pathway

2010 ◽  
Vol 38 (02) ◽  
pp. 373-386 ◽  
Author(s):  
Qin Hu ◽  
Ruile Pan ◽  
Liwei Wang ◽  
Bo Peng ◽  
Jingtian Tang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Ovarian Cancer Cells ◽  
Mitochondrial Cytochrome ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Platycodon Grandiflorum ◽  
Mitochondrial Cytochrome C

Platycodon grandiflorum (Jacq.) A. DC., a Chinese food and medicine, has been used as expectorant traditionally. The present study aimed to investigate the effect of Platycodon grandiflorum extract (PGE) on SKOV3 ovarian cancer cells. 3-(4,5- dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay was used to monitor cell numbers, Annexin-V/propidium iodide (PI) staining, RT-PCR and Western blot were used to examine cell apoptosis, caspases activation. Bcl-2 and Bax expressions and mitochondrial cytochrome c release. Our result showed that PGE-induced apoptosis was associated with activation of caspase-3, -8 and -9, down-regulation of Bcl-2, up-regulation of Bax and release of mitochondrial cytochrome c to cytosol. The data indicate that PGE may have anti-tumor effect mainly via caspase-3 and caspase-9 dependent apoptotic pathway.

Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver

2001 ◽  
Vol 281 (4) ◽  
pp. G1115-G1123 ◽  
Author(s):  
Junpei Soeda ◽  
Shinichi Miyagawa ◽  
Kenji Sano ◽  
Junya Masumoto ◽  
Shun'Ichiro Taniguchi ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Warm Ischemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dependent Manner ◽  
Mitochondrial Cytochrome ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Mitochondrial Cytochrome C

Apoptosis plays an important role in liver ischemia and reperfusion (I/R) injury. However, the molecular basis of apoptosis in I/R injury is poorly understood. The aims of this study were to ascertain when and how apoptotic signal transduction occurs in I/R injury. The apoptotic pathway in rats undergoing 90 min of warm ischemia with reperfusion was compared with that of rats undergoing prolonged ischemia alone. During ischemia, mitochondrial cytochrome c was released into the cytosol in a time-dependent manner in hepatocytes and sinusoidal endothelial cells, and caspase-3 and an inhibitor of caspase-activated DNase were cleaved. However, apoptotic manifestation and DNA fragmentation were not observed. After reperfusion, nuclear condensation, cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, and DNA fragmentation were observed and caspase-8 and Bid cleavage occurred. In contrast, prolonged ischemia alone induced necrosis rather than apoptosis. In summary, our results show that release of mitochondrial cytochrome c and caspase activation proceed during ischemia, although apoptosis is manifested after reperfusion.

scholarly journals Upregulation of Bcl-2 Through Caspase-3 Inhibition Ameliorates Ischemia/Reperfusion Injury in Rat Cardiac Allografts

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Jürg Grünenfelder ◽  
Douglas N. Miniati ◽  
Seiichiro Murata ◽  
Volkmar Falk ◽  
E. Grant Hoyt ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Reperfusion Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Myeloperoxidase Activity ◽  
Mitochondrial Cytochrome ◽  
Cytochrome C Release ◽  
Tnf Α ◽  
Cardiac Allografts ◽  
Mitochondrial Cytochrome C

Background Oxidative stress after ischemia/reperfusion of cardiac allografts leads to cytokine production. Bcl-2, an inhibitor of apoptosis, also has strong antioxidant properties. Caspase-3 is known to cleave bcl-2. This study tests the hypothesis that bcl-2 is downregulated while tumor necrosis factor-α (TNF-α) levels increase after cardiac transplantation. Furthermore, the use of caspase-3 inhibition was investigated as a strategy for preserving myocardial bcl-2 and mitochondrial cytochrome c after transplantation. Methods and Results PVG-to-ACI rat heterotopic cardiac transplantations were performed in 4 groups designed with 30 minutes’ ischemia and 4 or 8 hours of reperfusion (n=4 per group). Treatment consisted of DEVD-CHO 500 μg IP per animal to donor and recipient 2 hours before transplantation and 250 μg IC into allograft. Controls were treated with saline. Grafts were analyzed by reverse transcription–polymerase chain reaction for bcl-2 mRNA, by ELISA for TNF-α, for myeloperoxidase activity, and by Western blot for cytochrome c. In untreated groups, bcl-2 mRNA decreased significantly over time, whereas TNF-α increased significantly at 4 hours ( P =0.003) and returned to baseline after 8 hours’ reperfusion ( P =NS compared with normal hearts). Treatment with caspase-3 inhibitor showed significant upregulation of bcl-2 mRNA expression after 4 and 8 hours of reperfusion ( P <0.001 versus control), with a concomitant decrease in TNF-α to baseline levels. Myeloperoxidase activity in all groups was no different from that of normal hearts. Mitochondrial cytochrome c release increased in both control and treatment groups. Conclusions Bcl-2 is actively downregulated and TNF-α is upregulated in this model of cardiac allograft ischemia/reperfusion. Furthermore, the caspase-3 pathway is linked to this process, and blockade of caspase-3 can ameliorate reperfusion injury by upregulating bcl-2 and inhibiting TNF-α without affecting cytochrome c release.

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