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Source: Free Radical Biology and Medicine

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Total 199 results found since Jan 2013.

Evaluation of the role of Sigma 1 receptor and Cullin3 in retinal photoreceptor cells
Free Radic Biol Med. 2023 Jun 14:S0891-5849(23)00496-3. doi: 10.1016/j.freeradbiomed.2023.06.010. Online ahead of print.ABSTRACTSigma 1 receptor (Sig1R), a pluripotent modulator of cell survival, is neuroprotective in models of retinal degeneration when activated by the high-affinity, high-specificity ligand (+)-pentazocine ((+)-PTZ). The molecular mechanisms of Sig1R-mediated retinal neuroprotection are under investigation. We previously reported that the antioxidant regulatory transcription factor Nrf2 may be involved in Sig1R-mediated retinal photoreceptor cell (PRC) rescue. Cullin 3 (Cul3) is a component of the Nrf2-Ke...
Source: Free Radical Biology and Medicine - June 16, 2023 Category: Biology Authors: Jing Wang Shannon R Barwick Haiyan Xiao Sylvia B Smith Source Type: research

Hydroquinone regulates hemeoxygenase-1 expression via modulation of Src kinase activity through thiolation of cysteine residues.
In this study, we characterized the mechanism of the induction of hemeoxygenase (HO)-1 and other phase 2 enzymes by HQ and its derivatives. HQ upregulated the mRNA and protein levels of HO-1 by increasing the antioxidant-response element-dependent transcriptional activation of Nrf-2. Src knockdown or deficiency induced via siRNA treatment and infection with a retrovirus expressing shRNA targeting Src, as well as exposure to PP2, a Src kinase inhibitor, strongly abrogated HO-1 expression. Interestingly, HQ directly targeted and bound to the sulfhydryl group of cysteine-483 (C483) and C400 residues of Src, potentially leadin...
Source: Free Radical Biology and Medicine - January 2, 2013 Category: Biology Authors: Eun Byeon S, Yu T, Yang Y, Gyu Lee Y, Hye Kim J, Oh J, Yoon Jeong H, Hong S, Chul Yoo B, Cho WJ, Hong S, Youl Cho J Tags: Free Radic Biol Med Source Type: research

Willow bark extract increases antioxidant enzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans.
This study investigated the antioxidative effects of WBE in human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. WBE prevented oxidative-stress-induced cytotoxicity of HUVECs and death of C. elegans. WBE dose-dependently increased mRNA and protein expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) target genes heme oxygenase-1, γ-glutamylcysteine ligase modifier and catalytic subunits, and p62 and intracellular glutathione (GSH) in HUVECs. In the nematode C. elegans, WBE increased the expression of the gcs-1::green fluorescent protein reporter, a well-characterized target of...
Source: Free Radical Biology and Medicine - December 28, 2012 Category: Biology Authors: Ishikado A, Sono Y, Matsumoto M, Robida-Stubbs S, Okuno A, Goto M, King GL, Keith Blackwell T, Makino T Tags: Free Radic Biol Med Source Type: research

Loss of p53 in stromal fibroblasts promotes epithelial cell invasion through redox-mediated ICAM1 Signal.
Abstract Tumor microenvironment plays a major role in cancer development. Understanding how the stroma affects epithelial transformation will provide a basis for new preventive strategies. Recent evidences suggest that oxidative stress in stroma may play a role in cancer progression and loss of p53 function in the stromal cells were associated with poor prognosis and high tumor recurrence. However, the underlying mechanisms remain poorly understood. Here, we investigated the role of p53 loss in fibroblasts on epithelial transformation and the mechanistic involvement of reactive species. Using 3D-organotypic cultur...
Source: Free Radical Biology and Medicine - January 29, 2013 Category: Biology Authors: Trachootham D, Chen G, Zhang W, Lu W, Zhang H, Liu J, Huang P Tags: Free Radic Biol Med Source Type: research

Hypoxia downregulates PPARγ via an ERK 1/2-NF-κB-Nox4- dependent mechanism in human pulmonary artery smooth muscle cells.
Abstract The ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), regulates metabolism, cell proliferation, and inflammation. Pulmonary hypertension (PH) is associated with reduced PPARγ expression, and hypoxia exposure regimens that cause PH reduce PPARγ expression. The current study examines mechanisms of hypoxia-induced PPARγ downregulation in vitro and in vivo. Hypoxia reduced PPARγ mRNA and protein levels, PPARγ activity, and the expression of PPARγ-regulated genes in human pulmonary artery smooth muscle cells (HPASMC) exposed to 1% oxygen for 72hours. Simila...
Source: Free Radical Biology and Medicine - May 15, 2013 Category: Biology Authors: Lu X, Bijli KM, Ramirez A, Murphy TC, Kleinhenz J, Michael Hart C Tags: Free Radic Biol Med Source Type: research

Lung tumor growth-promoting function of peroxiredoxin 6.
This study compared lung tumor growth in PRDX6-overexpressing transgenic (Tg) mice and normal mice. These mice expressed elevated levels of PRDX6 mRNA and protein in multiple tissues. In vivo, Tg mice displayed a greater increase in the growth of lung tumor compared with normal mice. Glutathione peroxidase and calcium-independent phospholipase 2 (iPLA2) activities in tumor tissues of Tg mice were much higher than in tumor tissues of normal mice. Higher tumor growth in PRDX6-overexpressing Tg mice was associated with an increase in activating protein-1 (AP-1) DNA-binding activity. Moreover, expression of proliferating cell ...
Source: Free Radical Biology and Medicine - May 3, 2013 Category: Biology Authors: Jo M, Yun HM, Park KR, Hee Park M, Myoung Kim T, Ho Pak J, Jae Lee S, Moon DC, Park CW, Song S, Lee CK, Bae Han S, Tae Hong J Tags: Free Radic Biol Med Source Type: research

Integrin-linked kinase mediates the hydrogen peroxide-dependent transforming growth factor-β1 up-regulation.
Abstract Transforming growth factor type-β1 (TGF-β1) has been recognized as a central mediator in many pathological events related to extracellular matrix (ECM) proteins accumulation, where their locally increased expression has been implicated in the fibrosis process of numerous organs, including glomerular fibrosis in the kidney. We and others have reported the TGF-β1 synthesis regulation by reactive oxygen species (ROS), and moreover we also described the implication of integrin-linked kinase (ILK) in the AP-1-dependent TGF-β1 up-regulation. Thus, we propose here that H2O2-dependent TGF-β1 regulation may b...
Source: Free Radical Biology and Medicine - April 25, 2013 Category: Biology Authors: Gonzalez-Ramos M, de Frutos S, Griera M, Luengo A, Olmos G, Rodriguez-Puyol D, Calleros L, Rodriguez-Puyol M Tags: Free Radic Biol Med Source Type: research

The transcription factor Nrf2 promotes survival by enhancing the expression of uncoupling protein 3 under conditions of oxidative stress.
In conclusion, we have identified a novel regulatory process induced by an oxidative insult whereby the expression of the mitochondrial protein UCP3 is driven by the Nrf2 transcription factor, which decreases ROS production and prevents cell death. PMID: 23597505 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - April 16, 2013 Category: Biology Authors: Anedda A, López-Bernardo E, Acosta-Iborra B, Saadeh Suleiman M, Landázuri MO, Cadenas S Tags: Free Radic Biol Med Source Type: research

The role of the Nrf2-mediated defense system in corneal epithelial wound healing.
In this study, we investigated the role of the Nrf2-mediated defense system in corneal epithelial wound healing by using Nrf2-knockout (KO) mice. Nrf2 was expressed in the corneal epithelium of wild-type (WT) mice, but not in KO mice. Observation of wounds after 24h of healing revealed that healing of the corneal epithelium was significantly delayed in the Nrf2 KO mice, whereas Nrf2 was activated in the corneal epithelium of WT mice. Ki-67 staining revealed that the number of Ki-67-positive proliferating cells was significantly lower in the Nrf2 KO mice than in the WT mice at 24-36h after injury; however, these numbers wer...
Source: Free Radical Biology and Medicine - April 12, 2013 Category: Biology Authors: Hayashi R, Himori N, Taguchi K, Ishikawa Y, Uesugi K, Ito M, Duncan T, Tsujikawa M, Nakazawa T, Yamamoto M, Nishida K Tags: Free Radic Biol Med Source Type: research

Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1.
In this study we determined the molecular mechanisms of how homocysteine differentially affects receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) synthesis in the bone. The results showed that oxidative stress induced by homocysteine deranges insulin-sensitive FOXO1 and MAP kinase signaling cascades to decrease OPG and increase RANKL synthesis in osteoblast cultures. We observed that downregulation of insulin/FOXO1 and p38 MAP kinase signaling mechanisms due to phosphorylation of protein phosphatase 2A (PP2A) was the key event that inhibited OPG synthesis in homocysteine-treated osteoblast c...
Source: Free Radical Biology and Medicine - March 15, 2013 Category: Biology Authors: Vijayan V, Khandelwal M, Manglani K, Singh RR, Gupta S, Surolia A Tags: Free Radic Biol Med Source Type: research

Dimerumic acid attenuates receptor for advanced glycation endproducts signal to inhibit inflammation and diabetes mediated by Nrf2 activation and promotes methylglyoxal metabolism into d-lactic acid.
This study was designed to evaluate the effects of dimerumic acid (DMA) on receptor for advanced glycation endproducts (RAGE) signal activation and THP-1 monocyte inflammation treated with S100b, a specific ligand of RAGE. We found that DMA inhibited inflammatory cytokine production via upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and alleviated oxidative stress through attenuation of p47phox translocation to the membrane of S100b-treated THP-1 monocytes. We found that DMA activated Nrf2 mediated by the p38 kinase pathway in THP-1 monocytes. However, anti-inflammatory activity of DMA was attenuated by...
Source: Free Radical Biology and Medicine - May 23, 2013 Category: Biology Authors: Lee BH, Hsu WH, Hsu YW, Pan TM Tags: Free Radic Biol Med Source Type: research

Mechanism of protein decarbonylation.
Abstract Ligand/receptor-stimulation of cells promotes protein carbonylation that is followed by the decarbonylation process, which might involve thiol-dependent reduction (Wong et al., Circ. Res. 102 301-318, 2008). The present study further investigated the properties of this protein decarbonylation mechanism. We found that the thiol-mediated reduction of protein carbonyls is dependent on heat-labile biologic components. Cysteine and glutathione were found to be efficient substrates for decarbonylation. Thiols decreased the protein carbonyl content, as detected by 2,4-dinitrophenylhydrazine, but not the levels o...
Source: Free Radical Biology and Medicine - September 14, 2013 Category: Biology Authors: Wong CM, Marcocci L, Das D, Wang X, Luo H, Zungu-Edmondson M, Suzuki YJ Tags: Free Radic Biol Med Source Type: research

A functional link between heme oxygenase-1 and tristetraprolin in the anti-inflammatory effects of nicotine.
In this study, we sought to determine whether HO-1 associates with TTP to mediate the anti-inflammatory effects of nicotine. Inhibition of HO-1 activity or HO-1 expression attenuated the effects of nicotine on STAT3 activation, TTP induction, and TNF-α production in LPS-treated macrophages. Induction of HO-1 expression increased the level of TTP in the absence of nicotine. In a LPS-induced endotoxemia model, HO-1 deficiency blocked the effects of nicotine on the STAT3 phosphorylation, TTP induction and LPS-induced TNF-α production in the liver. Downregulation of STAT3 by siRNA attenuated the effect of nicotine on TTP exp...
Source: Free Radical Biology and Medicine - October 2, 2013 Category: Biology Authors: Uddin MJ, Joe Y, Zheng M, Blackshear PJ, Ryter SW, Park JW, Chung HT Tags: Free Radic Biol Med Source Type: research

Α-synuclein and mitochondrial bioenergetics regulate tetrahydrobiopterin levels in a human dopaminergic model of PD.
Abstract Parkinson's disease (PD) is a multi-factorial disease resulting in preferential death of the dopaminergic neurons in the substantia nigra. Studies of PD-linked genes and toxin-induced models of PD have implicated mitochondrial dysfunction, oxidative stress and the misfolding and aggregation of α-synuclein (α-syn) as key factors in disease initiation and progression. Many of these features of PD may be modelled in cells or animal models using the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Reducing oxidative stress and NOS activity have been shown to be protective in cell or animal models of MPP+ toxi...
Source: Free Radical Biology and Medicine - October 19, 2013 Category: Biology Authors: Ryan BJ, Lourenço-Venda L, Crabtree MJ, Hale AB, Channon KM, Wade-Martins R Tags: Free Radic Biol Med Source Type: research

Ferritin heavy chain as main mediator of preventive effect of metformin on mitochondrial damage induced by doxorubicin in cardiomyocyte.
In conclusion, these results deepen our knowledge of the protective action of MET against DOX-induced cardiotoxicity and suggest that therapeutic strategies based on FHC modulation could protect cardiomyocytes from the mitochondrial damage induced by DOX by restoring iron homeostasis. PMID: 24231192 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - November 11, 2013 Category: Biology Authors: Asensio-Lopez MC, Sanchez-Mas J, Pascual-Figal DA, de Torre C, Valdes M, Lax A Tags: Free Radic Biol Med Source Type: research