scholarly journals Brain age-dependent effects of acute endotoxemia on oxidative damage and mitochondrial function

2012 ◽  
Vol 1817 ◽  
pp. S97
Author(s):  
M.C. Cimolai ◽  
V. Vanasco ◽  
P. Evelson ◽  
H. Bugger ◽  
S. Alvarez
Keyword(s):  
Oxidative Damage ◽  
Mitochondrial Function ◽  
Age Dependent ◽  
Brain Age

scholarly journals The Effect of Voluntary Wheel Running on Muscle Mass, Mitochondrial Function and Oxidative Damage in Sod1???/???mice

2006 ◽  
Vol 38 (Suppl 1) ◽  
pp. S12
Author(s):  
Michael S. Lustgarten ◽  
Young C. Jang ◽  
Wook Song ◽  
Yuhong Liu ◽  
Anson Pierce ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Muscle Mass ◽  
Mitochondrial Function ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

scholarly journals Melatonin administration prevents cardiac and diaphragmatic mitochondrial oxidative damage in senescence-accelerated mice

2007 ◽  
Vol 194 (3) ◽  
pp. 637-643 ◽  
Author(s):  
M I Rodriguez ◽  
G Escames ◽  
L C López ◽  
J A García ◽  
F Ortiz ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Chronic Treatment ◽  
Melatonin Treatment ◽  
Mitochondrial Oxidative Stress ◽  
Melatonin Administration ◽  
Age Dependent ◽  
Mitochondrial Oxidative Damage ◽  
Senescence Accelerated Mice ◽  
Ratio Reduction

Cardiac and diaphragmatic mitochondria from male SAMP8 (senescent) and SAMR1 (resistant) mice of 5 or 10 months of age were studied. Levels of lipid peroxidation (LPO), glutathione (GSH), GSH disulfide (GSSG), and GSH peroxidase and GSH reductase (GRd) activities were measured. In addition, the effect of chronic treatment with the antioxidant melatonin from 1 to 10 months of age was evaluated. Cardiac and diaphragmatic mitochondria show an age-dependent increase in LPO levels and a reduction in GSH:GSSG ratios. Chronic treatment with melatonin counteracted the age-dependent LPO increase and GSH:GSSG ratio reduction in these mitochondria. Melatonin also increased GRd activity, an effect that may account for the maintenance of the mitochondrial GSH pool. Total mitochondrial content of GSH increased after melatonin treatment. In general, the effects of age and melatonin treatment were similar in senescence-resistant mice (SAMR1) and SAMP8 cardiac and diaphragmatic mitochondria, suggesting that these mice strains display similar mitochondrial oxidative damage at the age of 10 months. The results also support the efficacy of long-term melatonin treatment in preventing the age-dependent mitochondrial oxidative stress.

Activation of Mitochondrial STAT3 Increases Mitochondrial Respiration and Inhibits Oxidative Stress in Chronic Lymphocytic Leukemic Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 287-287 ◽  
Author(s):  
Li Jia ◽  
Nadiha Uddin ◽  
John G. Gribben
Keyword(s):  
Cell Death ◽  
Free Radical ◽  
Oxidative Damage ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Mitochondrial Mass ◽  
Free Radical Generation ◽  
Atp Turnover ◽  
Radical Generation

Abstract Abstract 287 Chronic lymphocytic leukemia (CLL) is a malignant disease occurring in the elderly and remains incurable. CLL is characterized by resistance to both spontaneous and induced apoptosis aided by changes induced by the tumor microenvironment. STAT3 is a signal responsive transcription factor that plays pivotal roles in tumorigensis in a number of malignancies including CLL. STAT3 resides in an inactive form in the cytoplasm of non-stimulated cells and in response to various cytokines and growth factors present in the microenvironment is activated through JAK-mediated phosphorylation of two residues, tyrosine 705 (Y705) and serine 727 (S727). Phosphorylation of this critical tyrosine residue (Y705) induces STAT3 dimerization through phosphotyrosine-SH2 domain interaction and. once dimerized, enters the nucleus and activates a broad array of target genes. The role of serine phosphorylation (S727) is less understood. It has been reported that STAT3 is constitutively phosphorylated on S727 and pS727-STAT3, not pY705-STAT3, binds DNA and activates transcription in CLL cells. However, it has also been reported that STAT3 is present in the mitochondria both in cell lines and primary liver and heart of mouse models, where it is one of the components of the mitochondrial electron transport chain (mETC) and plays an important role in mitochondrial respiration. The active form of mitochondrial STAT3 is pS727-STAT3 and it is crucial for Ras-dependent transformation by sustaining altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. It is unknown whether STAT3 regulates mitochondrial function in CLL. We therefore investigated whether activated STAT3 regulates mitochondrial respiration in CLL and whether it is important for CLL cell survival. Screening by Western blotting in untreated CLL patients' samples (n=16 )revealed that both pS727-STAT3 and pY705-STAT3 were constitutively expressed and we demonstrated correlation of the expression levels between these two active forms. Using fluorescent microscopy and cellular protein fractionation, both pS727-STAT3 and pY705-STAT3 showed mitochondrial localization in CLL cells. Stimulation of CLL cells with IL-10 induced STAT3 activation and both active forms of STAT3 exhibited mitochondrial translocation. The JAK inhibitor AG490 prevented STAT3 translocation to the mitochondria and led to reduction of mitochondrial mass and expression of cytochrome c oxidase IV (COX IV), one of the components of mETC. Knockdown of STAT3 RNA also decreased COX IV expression. Flow cytometry studies demonstrated that activation of STAT3 by IL-10 prevented depolarization of mitochondrial membrane potential and free radical generation by CLL cells, but inhibition of STAT3 induced mitochondrial oxidative damage and CLL cell death. The role of STAT3 activation by IL-10 on mitochondrial respiration was determined using a Seahorse XF Extracellular Flux Analyzer and demonstrated significantly increased coupled and uncoupled mitochondrial respiration and ATP turnover. Inhibition of STAT3 by AG490 reduced mitochondrial respiration and ATP turnover. However, decreased mitochondrial respiration did not provoke glycolytic capacity in CLL cells, indicating that CLL cells mainly rely on mitochondria for energetic needs. In summary, we demonstrate that activated STAT3 targets mitochondria and increases mitochondrial respiration and ATP turnover in CLL cells. This enables increased bioenergetic mitochondrial function and also prevents oxidative damage of CLL cells. Inhibition of STAT3 reduces mitochondrial mass and function but increases free radical generation and promotes CLL cell death. We therefore propose that mitochondrial STAT3 could be a therapeutic target for the treatment of CLL. Disclosures: Gribben: Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria.

scholarly journals Melatonin suppresses ER stress-dependent proapoptotic effects via AMPK in bone mesenchymal stem cells during mitochondrial oxidative damage

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chongxi Fan ◽  
Jianyu Feng ◽  
Chi Tang ◽  
Zhengbin Zhang ◽  
Yingtong Feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxidative Damage ◽  
Er Stress ◽  
Mitochondrial Function ◽  
Antioxidant Effect ◽  
Ampk Activation ◽  
Stress Injury ◽  
Oxidative Stress Injury

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) have been used as important cell-based tools for clinical applications. Oxidative stress-induced apoptosis causes a low survival rate after transplantation, and the underlying mechanisms remain unknown. The endoplasmic reticulum (ER) and mitochondria are vital organelles regulated by adenosine monophosphate (AMP)-activated protein kinase (AMPK), especially during oxidative stress injury. Melatonin exerts an antioxidant effect by scavenging free radicals. Here, we aimed to explore whether cytoprotective melatonin relieves ER stress-mediated mitochondrial dysfunction through AMPK in BMSCs after oxidative stress injury. Methods Mouse BMSCs were isolated and exposed to H2O2 in the absence or presence of melatonin. Thereafter, cell damage, oxidative stress levels, mitochondrial function, AMPK activity, ER stress-related proteins, and apoptotic markers were measured. Additionally, the involvement of AMPK and ER stress in the melatonin-mediated protection of BMSCs against H2O2-induced injury was investigated using pharmacologic agonists and inhibitors. Results Melatonin improved cell survival and restored mitochondrial function. Moreover, melatonin intimately regulated the phosphorylation of AMPK and molecules associated with ER stress pathways. AMPK activation and ER stress inhibition following melatonin administration improved the mitochondrial membrane potential (MMP), reduced mitochondria-initiated oxidative damage, and ultimately suppressed apoptotic signaling pathways in BMSCs. Cotreatment with N-acetyl-l-cysteine (NAC) significantly enhanced the antioxidant effect of melatonin. Importantly, pharmacological AMPK activation/ER stress inhibition promoted melatonin-induced cytoprotection, while pharmacological AMPK inactivation/ER stress induction conferred resistance to the effect of melatonin against H2O2 insult. Conclusions Our data also reveal a new, potentially therapeutic mechanism by which melatonin protects BMSCs from oxidative stress-mediated mitochondrial apoptosis, possibly by regulating the AMPK-ER stress pathway.

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