Abstract:
AIMS:Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. RESULTS:We demonstrate that Her2high cells and tumors have increased assembly of respiratory supercomplexes (SCs) and increased complex I-driven respiration in vitro and in vivo. They are also highly sensitive to MitoTam, a novel mitochondrial-targeted derivative of tamoxifen. Unlike tamoxifen, MitoTam efficiently suppresses experimental Her2high tumors without systemic toxicity. Mechanistically, MitoTam inhibits complex I-driven respiration and disrupts respiratory SCs in Her2high background in vitro and in vivo, leading to elevated reactive oxygen species production and cell death. Intriguingly, higher sensitivity of Her2high cells to MitoTam is dependent on the mitochondrial fraction of Her2. INNOVATION:Oncogenes such as HER2 can restructure ETC, creating a previously unrecognized therapeutic vulnerability exploitable by SC-disrupting agents such as MitoTam. CONCLUSION:We propose that the ETC is a suitable therapeutic target in Her2high disease. Antioxid. Redox Signal. 26, 84-103.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Rohlenova K,Sachaphibulkij K,Stursa J,Bezawork-Geleta A,Blecha J,Endaya B,Werner L,Cerny J,Zobalova R,Goodwin J,Spacek T,Alizadeh Pesdar E,Yan B,Nguyen MN,Vondrusova M,Sobol M,Jezek P,Hozak P,Truksa J,Rohlena J,Dodoi
10.1089/ars.2016.6677subject
Has Abstractpub_date
2017-01-10 00:00:00pages
84-103issue
2eissn
1523-0864issn
1557-7716journal_volume
26pub_type
杂志文章abstract::In the CNS, the heme oxygenase (HO) system has been reported to be active and to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge. We have recently shown that both curcumin and caffeic acid phenethyl ester, two phenolic natural compounds, potently induce HO-1 expression and acti...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2004.6.811
更新日期:2004-10-01 00:00:00
abstract:SIGNIFICANCE:Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. RECENT ADVANCES:Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy m...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6208
更新日期:2015-04-20 00:00:00
abstract::Increasing evidence indicates that disequilibrium of the alveolar oxidant-antioxidant balance may play a role in the pathogenesis of chronic fibrosing lung diseases. Excessive production of oxidants and a differential regulation of antioxidant enzymes have been described under these conditions. We characterized for th...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2105
更新日期:2009-02-01 00:00:00
abstract::Myocardial infarction triggers an inflammatory cascade that results in healing and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers innate immune mechanisms eliciting Toll-like receptor- mediated responses, activating the complement cascade and generating reactive oxygen species. Subsequent...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1907
更新日期:2006-11-01 00:00:00
abstract::Cells oxidize molecules to generate energy and to make the materials to build and support the structures and functions needed for life. However, unwanted oxidations can damage these same structures and impair function. Lipids (the lipids in membranes and lipoproteins) are targets of unwanted oxidations. The primary me...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308604773934396
更新日期:2004-06-01 00:00:00
abstract::Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various heart diseases. One of the most important mechanisms by which CoQ exerts cardioprotection is aerobic ATP production as a mobile electron carrier in the mitochondrial electron transfer chain. The ability of CoQ to afford myocardial protect...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601750100588
更新日期:2001-02-01 00:00:00
abstract:AIMS:Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities of reactive oxygen species (ROS) and resultant damage to mitochondrial enzymes is considered an important mechanism underlying reperfusion injury. Mitochondr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4698
更新日期:2013-11-01 00:00:00
abstract:SIGNIFICANCE:The accepted effects of aging in mammalian skeletal muscle are progressive atrophy and weakening, or sarcopenia. Canonical hallmarks of aging in skeletal muscle include a reduction in muscle fiber cross-sectional area, a loss in muscle fibers through apoptosis and denervation, and infiltration of connectiv...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3974
更新日期:2011-11-01 00:00:00
abstract:SIGNIFICANCE:Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. RECENT ADVANCES:Technical advances in th...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4393
更新日期:2012-09-01 00:00:00
abstract::Ischemia followed by reperfusion is the primary cause of tissue injury and infarction during heart attack and stroke. The initiating stimulus is believed to involve reactive oxygen species that are produced during reperfusion when electron transport resumes in the mitochondria after suppression by ischemia. Programmed...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1667
更新日期:2006-09-01 00:00:00
abstract:: Significance: Type 2 diabetes development involves multiple changes in β-cells, related to the oxidative stress and impaired redox signaling, beginning frequently by sustained overfeeding due to the resulting lipotoxicity and glucotoxicity. Uncovering relationships among t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7656
更新日期:2019-10-01 00:00:00
abstract::Chronic inflammation is a driving force for gastric carcinogenesis. Reactive oxygen species (ROS) generated during the inflammatory process generates DNA damage that is processed through the DNA repair pathways. In this study, we profiled key DNA repair proteins (single-strand-selective monofunctional uracil-DNA glyco...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4873
更新日期:2013-06-20 00:00:00
abstract::Although much is known about how TNF-alpha induces apoptosis in the presence of inhibitors of protein synthesis, little is known about how it induces apoptosis without these inhibitors. In this report we investigated temporal sequence of events induced by TNF-alpha in the absence of protein synthesis. Regardless of wh...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.3036
更新日期:2010-09-15 00:00:00
abstract:SIGNIFICANCE:The thioredoxin (Trx) superfamily proteins, including protein disulfide isomerases (PDI) and Dsb protein family, are major players in oxidative protein folding, which involves native disulfide bond formation. These proteins contain Trx folds with CXXC active sites and fulfill their physiological functions ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5849
更新日期:2014-07-20 00:00:00
abstract::Flavin-linked sulfhydryl oxidases participate in the net generation of disulfide bonds during oxidative protein folding in the endoplasmic reticulum. Members of the Quiescin-sulfhydryl oxidase (QSOX) family catalyze the facile direct introduction of disulfide bonds into unfolded reduced proteins with the reduction of ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3098
更新日期:2010-10-01 00:00:00
abstract:SIGNIFICANCE:Development of donor-specific antibodies (DSA) after kidney transplantation is associated with reduced allograft survival. A few strategies have been tested in controlled clinical trials for the treatment of antibody-mediated rejection (AMR), and no therapies are approved by regulatory authorities. Thus de...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5892
更新日期:2014-12-10 00:00:00
abstract::Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, complications of pregnancy, cognitive impairment, and osteoporosis. That elevated homocysteine leads to vascular dysfunction may be the linking factor between these apparently unrelated pathologies. Although a growing body of evidence sugge...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1809
更新日期:2007-11-01 00:00:00
abstract:SIGNIFICANCE:Mitochondrial function is central to a wide range of biological processes in health and disease and there is considerable interest in developing small molecules that are taken up by mitochondria and act as either probes of mitochondrial function or therapeutics in vivo. RECENT ADVANCES:Various strategies ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3969
更新日期:2011-12-15 00:00:00
abstract:SIGNIFICANCE:Half a century of research provided unambiguous proof that superoxide and species derived from it-reactive oxygen species (ROS)-play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5576
更新日期:2014-05-20 00:00:00
abstract::Mitochondrial ferritin (MtFt) is a newly identified H-ferritin-like protein expressed only in mitochondria. Previous studies have shown that its overexpression markedly affects intracellular iron homeostasis and rescues defects caused by frataxin deficiency. To assess how MtFt exerts its function under oxidative stres...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2306
更新日期:2009-08-01 00:00:00
abstract::It is well accepted that atherosclerosis occurs in a site-specific manner especially at branch points where disturbed blood flow (d-flow) predisposes to the development of plaques. Investigations both in vivo and in vitro have shown that d-flow is pro-atherogenic by promoting oxidative and inflammatory states in the a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3679
更新日期:2011-09-01 00:00:00
abstract:AIMS:Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. RESULTS:[Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. C...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2017.7239
更新日期:2018-05-10 00:00:00
abstract::Carica papaya Linn is widely known as a medicinal fruit. We sought to study a standardized fermented papaya preparation (FPP) for its effects on wound healing in adult obese diabetic (db/db) mice. FPP blunted the gain in blood glucose and improved the lipid profile after 8 weeks of oral supplementation. However, FPP d...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.3039
更新日期:2010-09-01 00:00:00
abstract::We previously reported a spontaneous development of type 2 diabetes-like phenotypes in glutathione peroxidase-1 (GPX1)-overexpressing (OE) mice. Diet restriction of these mice rescued all their phenotypes, except for hyperinsulinemia and hypersecretion of insulin. This study was to determine whether dietary Se deficie...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3295
更新日期:2011-02-01 00:00:00
abstract:SIGNIFICANCE:Pyridine dinucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), were discovered more than 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variet...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7120
更新日期:2018-01-20 00:00:00
abstract::This review focuses primarily on islet structural and functional changes related to an activated islet renin- angiotensin system (RAS), islet oxidative-redox imbalance, the concurrence of islet fibrosis (pericapillary, intra- and peri-islet), and islet amyloid deposition (pericapillary, intra- and peri-islet). The isl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1610
更新日期:2007-07-01 00:00:00
abstract:SIGNIFICANCE:Atrial fibrillation (AF) is a burgeoning health-care problem, and the currently available therapeutic armamentarium is barely efficient. Experimental and clinical evidence implicates inflammation and myocardial oxidative stress in the pathogenesis of AF. RECENT ADVANCES:Local and systemic inflammation has...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5542
更新日期:2014-03-10 00:00:00
abstract:SIGNIFICANCE:Once considered to be mere by-products of metabolism, reactive oxygen, nitrogen and sulfur species are now recognized to play important roles in diverse cellular processes such as response to pathogens and regulation of cellular differentiation. It is becoming increasingly evident that redox imbalance can ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7321
更新日期:2019-04-10 00:00:00
abstract::Selenium (Se) is an essential trace element in mammals that has been shown to exert its function through selenoproteins. Whereas optimal levels of Se in the diet have important health benefits, a recent clinical trial has suggested that supplemental intake of Se above the adequate level potentially may raise the risk ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3526
更新日期:2011-06-15 00:00:00
abstract::15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) is a cyclopentenone prostaglandin regarded as antiinflammatory mediator, which can act through peroxisome proliferator-activated receptor-gamma (PPARgamma) or through G protein-coupled surface receptors. It has been demonstrated that 15d-PGJ(2) potently increases t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2032
更新日期:2008-12-01 00:00:00