Abstract:
:Protection of ischemic myocardium is an important unmet need in reperfusion therapy of acute myocardial infarction. Myocardial ischemia and reperfusion induce necrosis and apoptosis in cardiomyocytes. Caspase processing and activation are critical steps in most receptor and nonreceptor pathways of apoptosis. Caspase inhibitors have been shown to reduce ischemia reperfusion injury in cardiac muscle. Information about dose response and time of administration are needed to optimize the design of preclinical studies. We used isolated adult rabbit cardiomyocytes subjected to metabolic inhibition (MI) and recovery to examine the role of caspases and caspase inhibitors, the dose response, and the timing of administration. In vitro inhibitory concentrations (Ki) were determined for purified caspases. Cardiomyocytes subjected to MI were treated with peptidomimetic fluoromethyl ketone inhibitors of caspases before or during MI, or at recovery. Caspase inhibitors were most effective when added before MI and included throughout recovery, but were partially protective if added after MI. The optimal concentration of the inhibitors tested was approximately 10 microM. Protection was sustained when cells were allowed to recover for 4 or 24 h. These results suggest that caspase activation is an important component of myocyte injury mediated by MI and recovery. Low doses of caspase inhibitors were identified that reduce injury in this model system, and further investigations using in vivo models are warranted.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Li HL,Karwatowska-Prokopczuk E,Mutomba M,Wu J,Karanewsky D,Valentino K,Engler RL,Gottlieb RAdoi
10.1089/152308601750100605keywords:
subject
Has Abstractpub_date
2001-02-01 00:00:00pages
113-23issue
1eissn
1523-0864issn
1557-7716journal_volume
3pub_type
杂志文章abstract:SIGNIFICANCE:Reactive oxygen species (ROS) are not only essential for the cell's normal functions, but also mediate many pathological effects. When cells experience oxidative stress, proteins are modulated by redox changes and ultimately generate novel signaling patterns. It remains elusive how proteins are modulated, ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4313
更新日期:2012-04-01 00:00:00
abstract:AIMS:S-glutathionylation of cysteine residues, catalyzed by glutathione S-transferase Pi (GSTP), alters structure/function characteristics of certain targeted proteins. Our goal is to characterize how S-glutathionylation of proteins within the endoplasmic reticulum (ER) impact cell sensitivity to ER-stress inducing dru...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6486
更新日期:2017-02-20 00:00:00
abstract:SIGNIFICANCE:Disturbance of glutathione (GSH) metabolism is a hallmark of numerous diseases, yet GSH functions are poorly understood. One key to this question is to consider its functional compartmentation. GSH is present in the endoplasmic reticulum (ER), where it competes with substrates for oxidation by the oxidativ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7148
更新日期:2017-11-20 00:00:00
abstract::BLNK (B cell linker protein) represents a central linker protein that bridges the B cell receptor-associated kinases with a multitude of signaling pathways. In this study, we have investigated the role of BLNK in oxidative stress signaling in B cells. H2O2 treatment of B cells induced a rapid tyrosine phosphorylation ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601317203576
更新日期:2001-12-01 00:00:00
abstract::The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/15230860260196326
更新日期:2002-06-01 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:SIGNIFICANCE:Chronic myeloid leukemia (CML) involves the malignant transformation of hematopoietic stem cells, defined largely by the Philadelphia chromosome and expression of the breakpoint cluster region-Abelson (BCR-ABL) oncoprotein. Pharmacological tyrosine kinase inhibitors (TKIs), including imatinib mesylate, hav...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6096
更新日期:2015-06-01 00:00:00
abstract::Although the essential role of selenium for cellular immune responses is obvious, delineation of the functions is lacking because selenium can either promote or inhibit cell growth, cytokine production, and activation of transcription factor nuclear factor-kappaB (NF-kappaB). Studies with human thioredoxin-1 (Trx-1)-t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.9.115
更新日期:2007-01-01 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:AIMS:Recent studies suggest that the molybdenum enzymes xanthine oxidase, aldehyde oxidase, and mARC exhibit nitrite reductase activity at low oxygen pressures. However, inhibition studies of xanthine oxidase in humans have failed to block nitrite-dependent changes in blood flow, leading to continued exploration for ot...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5397
更新日期:2015-08-01 00:00:00
abstract::Sirtuin-1 (SIRT1) is an NAD(+)-dependent protein deacetylase that is sensitive to oxidative signals. Our purpose was to determine whether SIRT1 activity is sensitive to the low molecular weight nitrosothiol, S-nitrosoglutathione (GSNO), which can transduce oxidative signals into physiological responses. SIRT1 formed m...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3251
更新日期:2010-10-01 00:00:00
abstract::In response to tissue damage and inflammation induced by a variety of xenobiotics including acetaminophen, carbon tetrachloride, ethanol, galactosamine, and endotoxin, as well as disease states such as viral hepatitis, and postischemic and regenerative injury, the liver produces large quantities of nitric oxide. Indee...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308601300185214
更新日期:2001-04-01 00:00:00
abstract::Exposure of neonatal rat cardiac myocytes to palmitate and glucose produces apoptosis as seen by cytochrome c release, caspase 3-like activation, DNA laddering, and poly(ADP-ribose) polymerase cleavage. The purpose of this study was to understand the role of reactive oxygen species in the initiation of programmed cell...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601750100524
更新日期:2001-02-01 00:00:00
abstract::Reactive oxygen species (ROS) can directly induce or enhance tumor necrosis factor (TNF)-mediated apoptosis in a number of different cell lines. To test the relevance of intracellular ROS in modulating apoptotic signaling in vivo, we evaluated hepatocellular apoptosis mediated by the TNF or Fas receptor in wild-type a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308602760598873
更新日期:2002-10-01 00:00:00
abstract:AIMS:Cystathionine β-synthase (CBS) catalyzes the first and rate-limiting step in the two-step trans-sulfuration pathway that converts homocysteine to cysteine. It is also one of three major enzymes responsible for the biogenesis of H2S, a signaling molecule. We have previously demonstrated that CBS is activated in cel...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2014.5891
更新日期:2015-02-10 00:00:00
abstract::The herbicide paraquat (PQ) has been implicated as a potential risk factor for the development of Parkinson's disease. In this study, PQ (0.5-1 microM) was shown to be selectively toxic to dopaminergic (DA) neurons through the activation of microglial NADPH oxidase and the generation of superoxide. Neuron-glia culture...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.654
更新日期:2005-05-01 00:00:00
abstract::The decision to remove or refold oxidized, denatured, or misfolded proteins by heat shock protein 70 and its binding partners is critical to determine cell fate under pathophysiological conditions. Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3300
更新日期:2011-05-15 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::Prospective epidemiological studies have shown that the incidence of numerous cardiovascular pathologies is correlated with body selenium status. However, it remains unclear whether selenium status also influences the outcome of myocardial infarction. The aim of the present study was to test whether dietary selenium i...
journal_title:Antioxidants & redox signaling
pub_type: 信件
doi:10.1089/1523086041361631
更新日期:2004-08-01 00:00:00
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-dependen...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.855
更新日期:2005-07-01 00:00:00
abstract::Studies from many laboratories have shown that overexpression of manganese superoxide dismutase (MnSOD) inhibits the growth of numerous tumor cell types. The inhibition of tumor cell growth can be attributed to the increase in the steady-state levels of H2O2 as a result of the increased dismuting activity of MnSOD. He...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860152409013
更新日期:2001-06-01 00:00:00
abstract:: Significance: Streptococcus pneumoniae (Spn), a facultative anaerobic Gram-positive human pathogen with increasing rates of penicillin and macrolide resistance, is a major cause of lower respiratory tract infections worldwide. Pneumococci are a primary agent of severe pneum...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7964
更新日期:2020-08-14 00:00:00
abstract::Reactive oxygen species (ROS) such as superoxide anion (O2-*) and hydrogen peroxide (H2O2) can be produced by vascular endothelium and smooth muscle cells under diverse physiological and pathophysiological situations. These species are known to exert various deleterious effects by which they might induce changes in va...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.2-363
更新日期:2000-07-01 00:00:00
abstract:AIMS:The immune system is critical for protection against infections and cancer, but requires scrupulous regulation to limit self-reactivity and autoimmunity. Our group has utilized a manganese porphyrin catalytic antioxidant (MnTE-2-PyP(5+), MnP) as a potential immunoregulatory therapy for type 1 diabetes. MnP has pre...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5167
更新日期:2013-12-01 00:00:00
abstract::Lipoic acid (LA) and its reduced product dihydrolipoic acid (DHLA) are potent antioxidants with capacity to scavenge reactive oxygen species (ROS) and recycle endogenous antioxidants. LA may increase cellular glutathione (GSH), an antioxidant lacking in the lung's epithelial lining fluid in lung disorders such as idio...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1890
更新日期:2008-02-01 00:00:00
abstract:AIM:Our previous studies have shown that NOD-like receptor protein (NALP3) inflammasome activation is importantly involved in podocyte dysfunction and glomerular sclerosis induced by hyperhomocysteinemia (hHcys). The present study was designed to test whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4666
更新日期:2013-05-01 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::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:SIGNIFICANCE:Nicotinamide adenine dinucleotide (NAD+) participates in redox reactions and NAD+-dependent signaling processes, which involve the cleavage of NAD+ coupled to posttranslational modifications of proteins or the production of second messengers. Either as a primary cause or as a secondary component of the pat...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7145
更新日期:2018-06-20 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