Abstract:
:The protein kinase C (PKC) isozyme family plays key roles in cell growth regulation and influences neoplastic disease development and progression. For example, PKCepsilon is oncogenic, and PKCdelta tumor-suppressive. PKC isozymes are characterized by distinct activation mechanisms entailing phosphatidylserine-dependent cofactor binding to the regulatory domain. Evidence is now emerging that redox signaling offers another platform of PKC regulation. We have established that PKC isozymes are regulated by S-thiolation, a posttranslational modification entailing disulfide linkage of low-molecular-weight species to select protein sulfhydryls. Our recent studies demonstrate that physiologically occurring disulfides with cysteinyl constituents, e.g., cystine, regulate cellular PKC isozymes by S-thiolation-triggered mechanisms. This report shows that PKC isozymes are also molecular targets of a chemically distinct class of disulfides. Disulfiram is a thiuram disulfide with potent cancer preventive activity in in vivo models of chemical carcinogenesis. Our results indicate that PKC Sthiolation by disulfiram induces differential regulatory effects on PKC isozymes that correlate with the cancer preventive activity of the drug. The implication of these findings is that PKC-regulatory effects of thiuram disulfides may offer a useful pharmacological guide for development of disulfiram analogues with superior cancer preventive activity.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Chu F,O'Brian CAdoi
10.1089/ars.2005.7.855keywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
855-62issue
7-8eissn
1523-0864issn
1557-7716journal_volume
7pub_type
杂志文章abstract:AIMS:Oxidative stress is thought to be involved in Friedreich's ataxia (FRDA), yet it has not been demonstrated in the target neurons that are first to degenerate. Using the YG8R mouse model of FRDA, microarray and neuritic growth experiments were carried out in the dorsal root ganglion (DRG), the primary site of neuro...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4537
更新日期:2013-11-01 00:00:00
abstract::Although there is an abundance of evidence suggesting that insulin resistance plays a significant role in the vasculature, the precise mechanistic role involved still remains unclear. In this review, we discuss the current background of insulin resistance in the context of insulin signaling and action in the vasculatu...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1053
更新日期:2005-07-01 00:00:00
abstract::Fluid shear stress is intimately linked with vascular oxidative stress and atherosclerosis. We posited that atherogenic oscillatory shear stress (OSS) induced mitochondrial superoxide (mtO2•-) production via NADPH oxidase and c-Jun NH(2)-terminal kinase (JNK-1 and JNK-2) signaling. In bovine aortic endothelial cells, ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3645
更新日期:2011-09-01 00:00:00
abstract:SIGNIFICANCE:Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metaboli...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6705
更新日期:2017-09-20 00:00:00
abstract::Oxidative stress plays a significant role in the pathogenesis of coronary artery disease (CAD). A p22(phox)-based NAD(P)H oxidase acts as a potent superoxide-generating system in the vasculature. We studied the association of the A640G and the C242T polymorphisms with clinical risk factors, endothelial function, and s...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860260220184
更新日期:2002-08-01 00:00:00
abstract::Molecular chaperones play key roles in protein quality control, signal transduction, proliferation, and cell death, and confer cytoprotection and assure survival after environmental stress. The heat-shock response is implicated in a variety of conditions including ischemic diseases, infection and immunity, neurodegene...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1866
更新日期:2008-01-01 00:00:00
abstract:AIMS:Mitochondrial thioredoxin reductase (Txnrd2) is a central player in the control of mitochondrial hydrogen peroxide (H2O2) abundance by serving as a direct electron donor to the thioredoxin-peroxiredoxin axis. In this study, we investigated the impact of targeted disruption of Txnrd2 on tumor growth. RESULTS:Tumor...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2014.5889
更新日期:2015-04-10 00:00:00
abstract:SIGNIFICANCE:There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5684
更新日期:2014-03-20 00:00:00
abstract::Oxidative stress due to increased epidermal levels of H(2)O(2) with consequent inhibition of catalase activity is generally accepted as a leading cytotoxic mechanism of melanocyte loss in vitiligo. Keratinocyte-derived cytokines are considered key factors in the maintenance of melanocyte structure and functions. We hy...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2976
更新日期:2010-09-01 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
abstract:SIGNIFICANCE:Autophagy is a fundamental cellular process that functions in the turnover of subcellular organelles and protein. Activation of autophagy may represent a cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5373
更新日期:2014-01-20 00:00:00
abstract:: Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including we...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8059
更新日期:2021-01-10 00:00:00
abstract::The current societal environment is marked by overabundant accessibility of food coupled with a strong trend of reduced physical activity, both leading to the development of a constellation of disorders, including central obesity, insulin resistance, dyslipidemia, and hypertension (metabolic syndrome). Prolonged calor...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3253
更新日期:2011-01-15 00:00:00
abstract:SIGNIFICANCE:The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiesc...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7273
更新日期:2018-07-10 00:00:00
abstract::Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPL...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2597
更新日期:2010-04-15 00:00:00
abstract:: Aims: Peroxisome is a critical organelle for fatty acid oxidation (FAO) and metabolism of reactive oxygen species (ROS). Increased oxidative stress in adipose tissue contributes to the development of insulin resistance and metabolic syndrome in obesity. This study aimed to...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7614
更新日期:2019-12-20 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:The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for can...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5733
更新日期:2014-08-10 00:00:00
abstract:: Significance: Heme oxygenase-1 (HO-1) is a ubiquitous 32-kDa protein expressed in many tissues and highly inducible. They catalyze the degradation of the heme group and the release of free iron, carbon monoxide, and biliverdin; the latter converted to bilirubin by biliverd...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7991
更新日期:2020-05-10 00:00:00
abstract::High affinity for NADH, and low affinity for NADPH, for reduction of endogenous coenzyme Q10 (CoQ10) by pig liver plasma membrane is reported in the present work. CoQ reduction in plasma membrane is carried out, in addition to other mechanisms, by plasma membrane coenzyme Q reductase (PMQR). We show that PMQR-catalyze...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.2-251
更新日期:2000-07-01 00:00:00
abstract::Gamma-interferon-inducible lysosomal thiol reductase (GILT) is constitutively expressed in most antigen presenting cells and is interferon γ inducible in other cell types via signal transducer and activator of transcription 1. Normally, N- and C-terminal propeptides are cleaved in the early endosome, and the mature pr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3684
更新日期:2011-08-01 00:00:00
abstract:: Aims: Lifelong pain is a hallmark feature of sickle cell disease (SCD). How sickle pathobiology evokes pain remains unknown. We hypothesize that increased cell-free heme due to ongoing hemolysis activates toll-like receptor 4 (TLR4), leading to the formation of reactive ox...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7913
更新日期:2021-02-01 00:00:00
abstract::Toxic renal failure induced by gentamicin, glycerol, or cisplatin, as well as ischemic renal failure in vivo and hypoxia/reoxygenation of tubular epithelial cells in vitro, induces the production of reactive oxygen metabolites (ROM). Generation of ROM is responsible for the induction of tubular epithelial cell death, ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308602762197452
更新日期:2002-12-01 00:00:00
abstract::Tissue oxygen plays a crucial role in maintaining tissue viability and in various diseases, including responses to therapy. Useful knowledge has been gained by methods that can give limited snapshots of tissue oxygen (e.g., oxygen electrodes) or evidence of a history of tissue hypoxia (e.g., EF5) or even indirect evid...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1635
更新日期:2007-08-01 00:00:00
abstract:: Significance: Metabolic syndrome (MetS) represents a cluster of cardiometabolic disorders, which accelerate the risk of developing diabetes, nonalcoholic fatty liver disease, and cardiovascular disorders such as atherosclerosis. Oxidative stress (OxS) and inflammation cont...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7994
更新日期:2021-01-20 00:00:00
abstract::Nuclear factor, erythroid 2 related factor 2 (Nrf2) belongs to the Cap'n'collar/basic region leucine zipper (CNC-bZIP) transcription factor family, and is activated by diverse oxidants, pro-oxidants, antioxidants, and chemopreventive agents. After phosphorylation and dissociation from the cytoplasmic inhibitor, Kelch-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.76
更新日期:2006-01-01 00:00:00
abstract::Membrane (lipid) rafts and caveolae, a subset of rafts, are cellular domains that concentrate plasma membrane proteins and lipids involved in the regulation of cell function. In addition to providing signaling platforms for G-protein-coupled receptors and certain tyrosine kinase receptors, rafts/caveolae can influence...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2365
更新日期:2009-06-01 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::Tumor necrosis factor (TNF) induces a caspase-independent but mitochondria-dependent cell death process in the mouse fibrosarcoma cell line L929. Mitochondria actively participate in this TNF-induced necrotic cell death by the generation of mitochondrial reactive oxygen species (ROS). The aim of this study was to iden...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.1999.1.3-285
更新日期:1999-10-01 00:00:00
abstract::Changes in the hemodynamic environment (e.g., hypertension, increased blood flow/shear stress) are known to lead to vascular remodeling; however, the underlying mechanisms by which hemodynamic forces control gene expression in vascular cells are not yet completely understood. This review considers how mechanosensitive...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1121
更新日期:2006-07-01 00:00:00