Recently published articles in
Free Radical Biology and Medicine

Role of Nitric Oxide and Nuclear Factor-Kappa B in the CYP2E1-Potentiation of Tumor Necrosis Factor Alpha Hepatotoxicity in Mice

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 19 November 2008
Defeng, Wu , Cijie, Xu , Arthur, Cederbaum
Thu, 20 Nov 2008 05:16:27 GMT

Homocysteine and inflammation as main determinants of oxidative stress in elderly

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 19 November 2008
Emilie, Ventura , Richard, Durant , Audrey, Jaussent , Marie-Christine, Picot , Marion, Morena , ...
Thu, 20 Nov 2008 05:16:27 GMT

Enhancement of PPAR-β activity by repetitive low-grade H2O2 stress protects HUVEC cells from subsequent oxidative stress-induced apoptosis

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 17 November 2008
Bimei, Jiang , Pengfei, Liang , Bin, Zhang , Xiaoyuan, Huang , Xianzhong, Xiao
Wed, 19 Nov 2008 05:16:51 GMT

Synergistic induction of heme oxygenase-1 by the components of an antioxidant supplement Protandim

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 17 November 2008
Kalpana, Velmurugan , Jawed, Alam , Joe M., McCord , Subbiah, Pugazhenthi
Wed, 19 Nov 2008 05:16:51 GMT

Editorial Board

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 11, 1 December 2008, Page IFC
[No author name available]
Tue, 18 Nov 2008 05:18:17 GMT

Announcements and Calendar

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 11, 1 December 2008, Page 1600
[No author name available]
Tue, 18 Nov 2008 05:18:17 GMT

Editorial Board

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Page IFC
[No author name available]
Sun, 16 Nov 2008 05:28:33 GMT

Nitrones as therapeutics

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1361-1374
Robert A., Floyd , Richard D., Kopke , Chul-Hee, Choi , Steven B., Foster , Sabrina, Doblas , ...

Nitrones have the general chemical formula X–CH=NO–Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones, including α-phenyl-tert-butylnitrone (PBN), have been shown to have potent biological activity in many experimental animal models. Many diseases of aging, including stroke, cancer development, Parkinson disease, and Alzheimer disease, are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development for stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several... Sun, 16 Nov 2008 05:28:33 GMT

Nrf2-induced antioxidant protection: A promising target to counteract ROS-mediated damage in neurodegenerative disease?

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1375-1383
Helga E., de Vries , Maarten, Witte , David, Hondius , Annemieke J.M., Rozemuller , Benjamin, Drukarch , ...

Neurodegenerative diseases share various pathological features, such as accumulation of aberrant protein aggregates, microglial activation, and mitochondrial dysfunction. These pathological processes are associated with generation of reactive oxygen species (ROS), which cause oxidative stress and subsequent damage to essential molecules, such as lipids, proteins, and DNA. Hence, enhanced ROS production and oxidative injury play a cardinal role in the onset and progression of neurodegenerative disorders. To maintain a proper redox balance, the central nervous system is endowed with an antioxidant defense mechanism consisting of endogenous antioxidant enzymes. Expression of most antioxidant enzymes is tightly controlled by the antioxidant response element... Sun, 16 Nov 2008 05:28:33 GMT

Covalent modification of proteins by green tea polyphenol (–)-epigallocatechin-3-gallate through autoxidation

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1384-1394
Takeshi, Ishii , Taiki, Mori , Tomoko, Tanaka , Daisuke, Mizuno , Ryoichi, Yamaji , ...

Green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG) has various beneficial properties including chemopreventive, anticarcinogenic, and antioxidant actions. The interaction with proteins known as EGCG-binding targets may be related to the anticancer effects. However, the binding mechanisms for this activity remain poorly understood. Using mass spectrometry and chemical detection methods, we found that EGCG forms covalent adducts with cysteinyl thiol residues in proteins through autoxidation. To investigate the functional modulation caused by binding of EGCG, we examined the interaction between EGCG and a thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Concentration-dependent covalent binding of EGCG to GAPDH was found to be coupled to the irreversible... Sun, 16 Nov 2008 05:28:33 GMT

Doxorubicin increases the susceptibility of brain mitochondria to Ca2+-induced permeability transition and oxidative damage

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1395-1402
Susana, Cardoso , Renato X., Santos , Cristina, Carvalho , Sónia, Correia , Gonçalo C., Pereira , ...

This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg−1), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced... Sun, 16 Nov 2008 05:28:33 GMT

Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1403-1412
Faisal, Thayyullathil , Shahanas, Chathoth , Abdulkader, Hago , Mahendra, Patel , Sehamuddin, Galadari

Evidence that curcumin may have anticancer activities has renewed interest in its potential to prevent and treat disease. In this study, we show that curcumin-mediated rapid generation of reactive oxygen species (ROS) leads to apoptosis by modulating different apoptotic pathways in mouse fibroblast L929 cells. We show for the first time that curcumin-induced rapid ROS generation causes the release of apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus, hence, leading to caspase 3-independent apoptosis. However, our studies also show that curcumin induces the release of cytochrome c from mitochondria, causing activation of caspase 3, and concomitant... Sun, 16 Nov 2008 05:28:33 GMT

Mutated glutathione-S-transferase reduced airway inflammation by limiting oxidative stress and Th2 response

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1413-1419
Prabhanshu, Tripathi , B.P., Singh , Naveen, Arora

Oxidative stress is an important factor in the pathogenesis of asthma. Furthermore, antioxidants like GST are reduced in asthma patients. In the present study, the therapeutic effects of exogenous GST and mGST were evaluated in a mice model. GST mutated at residues 21/27 has reduced IgE binding with similar enzyme activity as that of GST. To evaluate the therapeutic effects of GST, BALB/c mice were immunized and challenged with ovalbumin. Mice were given GST, mGST, and α-lipoic acid by inhalation and sacrificed on Day 31 to evaluate inflammation and oxidative stress. Mice treated with mGST showed significantly reduced total cell... Sun, 16 Nov 2008 05:28:33 GMT

Oxidative damage in brain from human mutant APP/PS-1 double knock-in mice as a function of age☆

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1420-1425
Hafiz Mohmmad, Abdul , Rukhsana, Sultana , Daret K., St. Clair , William R., Markesbery , D. Allan, Butterfield

Oxidative stress is strongly implicated in the progressive decline of cognition associated with aging and neurodegenerative disorders. In the brain, free radical-mediated oxidative stress plays a critical role in the age-related decline of cellular function as a result of the oxidation of proteins, lipids, and nucleic acids. A number of studies indicate that an increase in protein oxidation and lipid peroxidation is associated with age-related neurodegenerative diseases and cellular dysfunction observed in aging brains. Oxidative stress is one of the important factors contributing to Alzheimer’s disease (AD), one of whose major hallmarks includes brain depositions of amyloid beta-peptide (Aβ) derived... Sun, 16 Nov 2008 05:28:33 GMT

A novel fluorescent probe for the detection of nitric oxide in vitro and in vivo

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1426-1436
Jie, Ouyang , Hao, Hong , Chao, Shen , Yong, Zhao , Chenguang, Ouyang , ...
Sun, 16 Nov 2008 05:28:33 GMT

Induction of adaptive response and enhancement of PC12 cell tolerance by lipopolysaccharide primarily through the upregulation of glutathione S-transferase A3 via Nrf2 activation

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1437-1445
Yo, Omata , Yoshiro, Saito , Katsuhide, Fujita , Yoko, Ogawa , Keiko, Nishio , ...
Sun, 16 Nov 2008 05:28:33 GMT

Oxidative stress and chronological aging in glycogen-phosphorylase-deleted yeast☆

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1446-1456
Cristián, Favre , Pablo S., Aguilar , María C., Carrillo
Sun, 16 Nov 2008 05:28:33 GMT

Carbonyl scavenger and antiatherogenic effects of hydrazine derivatives

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1457-1467
Sylvain, Galvani , Christelle, Coatrieux , Meyer, Elbaz , Marie-Hélène, Grazide , Jean-Claude, Thiers , ...

Reactive carbonyl compounds (RCC) generated by polyunsaturated fatty acid oxidation alter progressively cellular and tissular proteins by forming adducts on free amino groups and thiol residues (carbonyl stress). Carbonyl scavengers may neutralize RCC, but their protective effect in atherosclerosis has not been extensively studied. We report the carbonyl scavenger and antiatherogenic properties of hydrazine derivatives, namely hydralazine, an antihypertensive drug, isoniazid, an antituberculosis agent, and two antidepressants, phenelzine and iproniazid. These drugs were poorly efficient in preventing the oxidation of LDL mediated by smooth muscle cells (SMCs), but inhibited the toxicity of UV-oxidized LDL (oxLDL) and of 4-hydroxynonenal (4-HNE). Hydrazine... Sun, 16 Nov 2008 05:28:33 GMT

Constriction of pulmonary artery by peroxide: role of Ca2+ release and PKC

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1468-1476
Ghazaleh Esmaeil, Pourmahram , Vladimir A., Snetkov , Yasin, Shaifta , Svetlana, Drndarski , Greg A., Knock , ...

Reactive oxygen species are implicated in pulmonary hypertension and hypoxic pulmonary vasoconstriction. We examined the effects of low concentrations of peroxide on intrapulmonary arteries (IPA). IPAs from Wistar rats were mounted on a myograph for recording tension and estimating intracellular Ca2+ using Fura-PE3. Ca2+ sensitization was examined in α-toxin-permeabilized IPAs, and phosphorylation of MYPT-1 and MLC20 was assayed by Western blot. Peroxide (30 μM) induced a vasoconstriction with transient and sustained components and equivalent elevations of intracellular Ca2+. The transient constriction was strongly suppressed by indomethacin, the TP-receptor antagonist SQ-29584, and the Rho kinase inhibitor Y-27632, whereas sustained constriction was unaffected.... Sun, 16 Nov 2008 05:28:33 GMT

Redox modulation inhibits CD8 T cell effector function

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1477-1486
Martha M., Sklavos , Hubert M., Tse , Jon D., Piganelli

The evolutionary preservation of reactive oxygen species in innate immunity underscores the important roles these constituents play in immune cell activity and as signaling intermediates. In an effort to exploit these pathways to achieve control of aberrant immune activation we demonstrate that modulation of redox status suppresses cell proliferation and production of IL-2, IFN-γ, TNF-α, and IL-17 in two robust CD8 T-cell-dependent in vitro mouse models: (1) response to alloantigen in an mixed leukocyte reaction and (2) CD8 T cell receptor transgenic OT-1 response to cognate peptide (SIINFEKL). To correlate these findings with cytotoxic lymphocyte (CTL) function we performed cytotoxicity... Sun, 16 Nov 2008 05:28:33 GMT

4-Hydroxynonenal enhances MMP-2 production in vascular smooth muscle cells via mitochondrial ROS-mediated activation of the Akt/NF-κB signaling pathways

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1487-1492
Seung J., Lee , Kyo W., Seo , Mi R., Yun , Sun S., Bae , Won S., Lee , ...

4-Hydroxynonenal (HNE) accumulates at atherosclerotic lesions, but its role in the progression of atherosclerosis is not clear. Considering the role of matrix metalloproteinases (MMP) in plaque destabilization, we investigated the mechanism by which HNE induces MMP production in vascular smooth muscle cells (VSMC). VSMC stimulated by HNE (1.0 μM) produced enzymatically active MMP-2 with an increased promoter activity, which was abolished by mutation of the NF-κB binding site in the promoter region. The increased NF-κB activity with subsequent MMP-2 production by HNE was significantly attenuated by transfection with Akt siRNA as well as by pretreatment with the PI3K/Akt inhibitors LY294002 (10 μM)... Sun, 16 Nov 2008 05:28:33 GMT

Increased oxidative stress and astrogliosis responses in conditional double-knockout mice of Alzheimer-like presenilin-1 and presenilin-2

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Pages 1493-1499
Manjie, Zhu , Feng, Gu , Jianting, Shi , Jinfeng, Hu , Yinghe, Hu , ...

Conditional presenilin 1 and presenilin 2 double knockout causes memory dysfunction and reproduces neurodegenerative phenotypes of Alzheimer disease (AD) in mice. Oxidative stress has been long implicated predominantly in amyloidosis-mediated AD pathologies; however, its role in response to the loss-of-function pathogenic mechanism of AD remains unclear. In this study, we examined the oxidative stress status in PS1 and PS2 double-knockout (PS cDKO) mice using F2-isoprostanes (iPF2α-III) as the marker of lipid peroxidation. Lipid peroxidation was enhanced in a gender- and age-related manner in the PS cDKO mice independent of brain Aβ deposition. Such oxidative abnormalities predominantly in cerebral cortex at... Sun, 16 Nov 2008 05:28:33 GMT

Announcements and Calendar

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 10, 15 November 2008, Page 1500
[No author name available]
Sun, 16 Nov 2008 05:28:33 GMT

TNF-induced mitochondrial damage: A link between mitochondrial complex I activity and left ventricular dysfunction

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 12 November 2008
Nithya, Mariappan , Carrie M., Elks , Bruno, Fink , Joseph, Francis
Sun, 16 Nov 2008 05:28:33 GMT

S-Nitrosylation of the Epidermal Growth Factor Receptor: A Regulatory Mechanism of the Receptor Tyrosine Kinase Activity

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 11 November 2008
Maribel, Murillo-Carretero , Ana, Torroglosa , Carmen, Castro , Antonio, Villalobo , Carmen, Estrada
Sun, 16 Nov 2008 05:28:33 GMT

Relationship between oxidative stress and HIF-1α mRNA during sustained hypoxia in humans

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 10 November 2008
Vincent, Pialoux , Rémi, Mounier , Allison D., Brown , Craig D., Steinback , Jean, Rawling , ...
Sun, 16 Nov 2008 05:28:33 GMT

Immuno-spin-trapping of a post-translational carboxypeptidase B1 radical formed by a dual role of xanthine oxidase and endothelial nitric oxide synthase in acute septic mice

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 7 November 2008
Saurabh, Chatterjee , Marilyn, Ehrenshaft , Suchandra, Bhattacharjee , Leesa J., Deterding , Marcelo G., Bonini , ...
Sun, 16 Nov 2008 05:28:33 GMT

Iron-Enhanced Paraquat-Mediated Dopaminergic Cell Death Due to Increased Oxidative Stress as a Consequence of Microglial Activation

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 7 November 2008
Jun, Peng , Fang Feng, Stevenson , May Lin, Oo , Julie K., Andersen
Sun, 16 Nov 2008 05:28:33 GMT

Polymerized placenta hemoglobin attenuates ischemia/reperfusion injury and restores the nitroso-redox balance in isolated rat heart

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 November 2008
Tao, Li , Jing, Li , Jin, Liu , Pu, Zhang , Wei, Wu , ...
Sun, 16 Nov 2008 05:28:33 GMT

Oxidative stress induces macroautophagy of amyloid β–protein and ensuing apoptosis

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 November 2008
Lin, Zheng , Katarina, Kågedal , Nodi, Dehvari , Eirikur, Benedikz , Richard, Cowburn , ...
Sun, 16 Nov 2008 05:28:33 GMT

Amplifying the fluorescence of bilirubin enables the real-time detection of heme oxygenase activity

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 6 November 2008
Roman, Klemz , Mir-Farzin, Mashreghi , Claudia, Spies , Hans-Dieter, Volk , Katja, Kotsch
Sun, 16 Nov 2008 05:28:33 GMT

Nrf2 regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 5 November 2008
C.J., Harvey , R.K., Thimmulappa , A., Singh , D.J., Blake , G., Ling , ...
Sun, 16 Nov 2008 05:28:33 GMT

Significant Longevity-extending Effects of EGCG on C. Elegans under Stresses

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 5 November 2008
Longze, Zhang , Guoliang, Jie , Junjing, Zhang , Baolu, Zhao
Sun, 16 Nov 2008 05:28:33 GMT

Induction of apoptosis in a human leukemic cell line via reactive oxygen species modulation by antioxidants

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Uncorrected Proof, Available online 1 November 2008
Tullia, Maraldi , Cecilia, Prata , Diana, Fiorentini , Laura, Zambonin , Laura, Landi , ...

In the human acute myeloid leukemia cell line M07e, the growth factor interleukin-3 (IL-3) induces ROS formation, positively affecting Glut1-mediated glucose uptake and cell survival. The effect of IL-3 and exogenous hydrogen peroxide on cell viability seems to be mediated through inhibition of the cell death commitment, as shown by apoptotic markers such as caspase activities, apoptotic nuclei, and changes in the amount of proteins belonging to the Bcl-2 family. The pivotal role of ROS is confirmed using various antioxidants, such as EUK-134, ebselen, TEMPO, and hydroxylamine probe. In fact, these antioxidants, acting through different mechanisms, decrease glucose transport activity... Sun, 16 Nov 2008 05:28:33 GMT

Editorial Board

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Page IFC
[No author name available]
Sun, 16 Nov 2008 05:28:33 GMT

Jason D. Morrow, M.D. (1957–2008)

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1203-1204
L. Jackson, Roberts, II II
Sun, 16 Nov 2008 05:28:33 GMT

20-HETE and F2-isoprostanes in the metabolic syndrome: the effect of weight reduction

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Uncorrected Proof, Available online 1 November 2008
I-Jung, Tsai , Kevin D., Croft , Trevor A., Mori , John R., Falck , Lawrence J., Beilin , ...

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that regulates vascular function and sodium homeostasis. Studies showing an association between 20-HETE excretion, raised BMI, and oxidative stress suggest that 20-HETE may be important in the development of cardiovascular disease in the metabolic syndrome (MetS). We investigated whether 20-HETE and F2-isoprostanes (markers of oxidative stress) were altered in the MetS before and after weight reduction. A case-controlled comparison of 30 participants with the MetS and matched controls showed that plasma and urinary 20-HETE and F2-isoprostanes were significantly elevated in the MetS group. There was a significant gender×group interaction... Sun, 16 Nov 2008 05:28:33 GMT

Regulation of cellular signals from nutritional molecules: a specific role for phytochemicals, beyond antioxidant activity

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1205-1216
Fabio, Virgili , Maria, Marino

Phytochemicals (PhC) are a ubiquitous class of plant secondary metabolites. A “recommended” human diet should warrant a high proportion of energy from fruits and vegetables, therefore providing, among other factors, a huge intake of PhC, in general considered “health promoting” by virtue of their antioxidant activity and positive modulation, either directly or indirectly, of the cellular and tissue redox balance. Diet acts through multiple pathways and the association between the consumption of specific food items and the risk of degenerative diseases is extremely complex. Recent literature suggests that molecules having a chemical structure compatible with a putative antioxidant capacity can... Sun, 16 Nov 2008 05:28:33 GMT

Evidence for NQO2-mediated reduction of the carcinogenic estrogen ortho-quinones

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Corrected Proof, Available online 1 November 2008
Nilesh W., Gaikwad , Li, Yang , Eleanor G., Rogan , Ercole L., Cavalieri

The physiological function of NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase) is to detoxify potentially reactive quinones by direct transfer of two electrons. A similar detoxification role has not been established for its homologue NRH:quinone oxidoreductase 2 (NQO2). Estrogen quinones, including estradiol(E2)-3,4-Q, generated by estrogen metabolism, are thought to be responsible for estrogen-initiated carcinogenesis. In this investigation, we have shown for the first time that NQO2 catalyzes the reduction of electrophilic estrogen quinones and thereby may act as a detoxification enzyme. ESI and MALDI mass spectrometric binding studies involving E2-3,4-Q with NQO2 clearly support the formation of an enzyme–substrate physical complex. The problem... Sun, 16 Nov 2008 05:28:33 GMT

Nrf2 Dependent Sulfiredoxin-1 Expression Protects Against Cigarette Smoke-induced Oxidative Stress in Lungs

Publication year: 2008
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 1 November 2008
Anju, Singh , Guoyu, Ling , Avvaru N., Suhasini , Ping, Zhang , Masayuki, Yamamoto , ...
Sun, 16 Nov 2008 05:28:33 GMT

“ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis”—a critical commentary

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1217-1219
Jacek, Zielonka , B., Kalyanaraman

In a recent publication (K. Ishikawa et al., 2008, Science 320, 661–664), the authors described how replacing the endogenous mitochondrial DNA (mtDNA) in a weakly metastatic mouse tumor cell line with mtDNA from a highly metastatic cell line enhanced tumor progression through enhanced production of reactive oxygen species (ROS). The authors attributed the transformation from a low-metastatic cell line to a high-metastatic phenotype to overproduction of ROS (hydrogen peroxide and superoxide) caused by a dysfunction in mitochondrial complex I protein encoded by mtDNA transferred from the highly metastatic tumor cell line. In this critical evaluation, using the paper by Ishikawa... Sun, 16 Nov 2008 05:28:33 GMT

A twist in the tail: synergism between mitochondria and NADPH oxidase in the hypoxia-induced elevation of reactive oxygen species in pulmonary artery☆

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1220-1222
Jeremy P.T., Ward
Sun, 16 Nov 2008 05:28:33 GMT

Hypoxia activates NADPH oxidase to increase [ROS]i and [Ca2+]i through the mitochondrial ROS-PKCɛ signaling axis in pulmonary artery smooth muscle cells

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1223-1231
Rakesh, Rathore , Yun-Min, Zheng , Chun-Feng, Niu , Qing-Hua, Liu , Amit, Korde , ...

The importance of NADPH oxidase (Nox) in hypoxic responses in hypoxia-sensing cells, including pulmonary artery smooth muscle cells (PASMCs), remains uncertain. In this study, using Western blot analysis we found that the major Nox subunits Nox1, Nox4, p22phox, p47phox, and p67phox were equivalently expressed in mouse pulmonary and systemic (mesenteric) arteries. However, acute hypoxia significantly increased Nox activity and translocation of p47phox protein to the plasma membrane in pulmonary, but not mesenteric, arteries. The Nox inhibitor apocynin and p47phox gene deletion attenuated the hypoxic increase in intracellular concentrations of reactive oxygen species and Ca2+ ([ROS]i and [Ca2+]i), as well as... Sun, 16 Nov 2008 05:28:33 GMT

Bz-423 superoxide signals apoptosis via selective activation of JNK, Bak, and Bax☆

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1232-1242
Neal B., Blatt , Anthony E., Boitano , Costas A., Lyssiotis , Anthony W., Opipari Jr. , Gary D., Glick

Bz-423 is a proapoptotic 1,4-benzodiazepine with potent therapeutic properties in murine models of lupus and psoriasis. Bz-423 modulates the F1F0-ATPase, inducing the formation of superoxide within the mitochondrial respiratory chain, which then functions as a second messenger initiating apoptosis. Herein, we report the signaling pathway activated by Bz-423 in mouse embryonic fibroblasts containing knockouts of key apoptotic proteins. Bz-423-induced superoxide activates cytosolic ASK1 and its release from thioredoxin. A mitogen-activated protein kinase cascade follows, leading to the specific phosphorylation of JNK. JNK signals activation of Bax and Bak which then induces mitochondrial outer membrane permeabilization to cause the release of... Sun, 16 Nov 2008 05:28:33 GMT

Telomerase deficiency promotes oxidative stress by reducing catalase activity

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1243-1251
Gema, Pérez-Rivero , María P., Ruiz-Torres , María L., Díez-Marqués , Andrés, Canela , José M, López-Novoa , ...

Telomere shortening and redox imbalance have been related to the aging process. We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking telomerase activity (Terc−/−) to analyze the redox balance and the functional consequences promoted by telomerase deficiency. Comparison with wild-type (WT) MEF showed that Terc−/− MEF had greater oxidant damage, showing higher superoxide anion and hydrogen peroxide production and lower catalase activity. Restoration of telomerase activity in Terc−/− MEF increased catalase expression and activity. TGF-β1 and collagen type IV levels were higher in Terc−/− than in WT MEF. TGF-β1 promoter activity decreased when Terc−/− MEF were incubated with... Sun, 16 Nov 2008 05:28:33 GMT

The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1252-1262
Lorena, Arranz , Cesáreo, Fernández , Antonio, Rodríguez , José Manuel, Ribera , Mónica, De la Fuente
Sun, 16 Nov 2008 05:28:33 GMT

Commonalities of genetic resistance to spontaneous autoimmune and free radical-mediated diabetes

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1263-1270
Jing, Chen , Ying, Lu , Chul-Ho, Lee , Renhua, Li , Edward H., Leiter , ...

ALR/Lt, a NOD-related mouse strain, was selected for resistance to alloxan free radical-mediated diabetes (ALD). Despite extensive genomic identity with NOD (>70%), ALR mice display strong resistance to autoimmune type 1 diabetes (T1D) due to both an unusual elevation in systemic antioxidant defenses and a reduction in cellular ROS production that extends to the beta cell level. Reciprocal backcross to NOD previously linked the ALR-derived T1D resistance to Chr. 3, 8, and 17 as well as to the ALR mt-Nd2a allele encoded by the mitochondrial genome (mtDNA). To determine whether any of the ALR-derived loci protecting against T1D also protected... Sun, 16 Nov 2008 05:28:33 GMT

A pulse-radiolysis approach to fast reductive cleavage of a disulfide bond to uncage enzyme activity

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1271-1278
Lilia, Milanesi , Salvador, Tomas , Christopher A., Hunter , Julia A., Weinstein , Ruth, Edge , ...

The essential thiol of the enzyme papain has been caged by linking to an aromatic thiol. The resulting caged protein is inactive but enzymatic activity is fully restored upon chemical cleavage of the protective disulfide bond. We have exploited the chemistry of this disulfide bond to uncage papain by pulse radiolysis. We have shown that up to 10% of the enzyme activity can be restored by reductive pulse radiolysis. This approach has been tested on a small-molecule model system, and experiments on this model compound show that pulse radiolysis of the mixed cysteine-aromatic disulfide results in selective reduction of the... Sun, 16 Nov 2008 05:28:33 GMT

Separation, detection, and quantification of hydroperoxides formed at side-chain and backbone sites on amino acids, peptides, and proteins

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1279-1289
Philip E., Morgan , David I., Pattison , Clare L., Hawkins , Michael J., Davies

Hydroperoxides are major reaction products of radicals and singlet oxygen with amino acids, peptides, and proteins. However, there are few data on the distribution of hydroperoxides in biological samples and their sites of formation on peptides and proteins. In this study we show that normal-or reversed-phase gradient HPLC can be employed to separate hydroperoxides present in complex systems, with detection by postcolumn oxidation of ferrous xylenol orange to the ferric species and optical detection at 560 nm. The limit of detection (10–25 pmol) is comparable to chemiluminescence detection. This method has been used to separate and detect hydroperoxides, generated by... Sun, 16 Nov 2008 05:28:33 GMT

Insights into the effects of α-synuclein expression and proteasome inhibition on glutathione metabolism through a dynamic in silico model of Parkinson's disease: validation by cell culture data

Publication year: 2008
Source: Free Radical Biology and Medicine, Volume 45, Issue 9, 1 November 2008, Pages 1290-1301
Shireen, Vali , Shankar J., Chinta , Jun, Peng , Zeba, Sultana , Neetu, Singh , ...

Dopaminergic neurodegeneration during Parkinson disease (PD) involves several pathways including proteasome inhibition, α-synuclein (α-syn) aggregation, mitochondrial dysfunction, and glutathione (GSH) depletion. We have utilized a systems biology approach and built a dynamic model to understand and link the various events related to PD pathophysiology. We have corroborated the modeling data by examining the effects of α-syn expression in the absence and presence of proteasome inhibition on GSH metabolism in dopaminergic neuronal cultures. We report here that the expression of the mutant A53T form of α-syn is neurotoxic and causes GSH depletion in cells after proteasome inhibition, compared to wild-type α-syn-expressing... Sun, 16 Nov 2008 05:28:33 GMT