Protein transduction of an antioxidant enzyme: subcellular localization of superoxide dismutase fusion protein in cells

Kim, Dae Won; Kim, So Young; Lee, Sun Hwa; Lee, Yeum Pyo; Lee, Min Jung; Jeong, Min Seop; Jang, Sang Ho; Park, Jinseu; Lee, Kil Soo; Kang, Tae‐Cheon; Won, Moo Ho; Cho, Sung‐Woo; Kwon, Oh Nam; Eum, Won Sik; Choi, Soo Young

doi:10.5483/bmbrep.2008.41.2.170

Cited by 10 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Superoxide dismutase (SOD) activity was measured by monitoring inhibition of the ferricytochrome c reduction reaction by xanthine/xanthine oxidase, as described previously (Kim et al 2008). The reaction mixture contained 10 lM cytochrome c, 50 lM xanthine, and sufficient xanthine oxidase to produce a reduction rate of cytochrome c of 0.025 absorbance units per min at 550 nm.…”

Section: Oxidative Stress Parametersmentioning

confidence: 99%

Neuroprotective Effects of 2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Against Oxidative Stress

Kim

Son

et al. 2011

Cell Mol Neurobiol

Self Cite

View full text Add to dashboard Cite

Oxidative stress, glutamate excitotoxicity, and inflammation are the important pathological mechanisms in neurodegenerative diseases. Recently, we reported that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects rat glial cells against glutamate-induced excitotoxicity. In this study, we report the effects of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride on primary cultured cortical astrocytes after exposure to hydrogen peroxide (H₂O₂). Pretreatment of cells with 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride prior to H₂O₂ exposure attenuated the H₂O₂-induced reductions in cell survival and superoxide dismutase, catalase, glutathione, and glutathione peroxidase activities. It also reduced H₂O₂-induced increases in reactive oxygen species levels, malondialdehyde content, and production of nitric oxide. These effects were all concentration-dependent. Our results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects against oxidative stress.

show abstract

Section: Oxidative Stress Parametersmentioning

confidence: 99%

Neuroprotective Effects of 2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Against Oxidative Stress

Kim

Son

et al. 2011

Cell Mol Neurobiol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Admittedly, our knowledge of the role of endothelial ROS in pathology remains limited [105,106], in part due to lack of site-specific antioxidant interventions [107]. Nevertheless, endothelial uptake and effects of PEG–AOE are no better than those of naked AOEs in vitro and in vivo [16].…”

Section: Targeted Interception Of Ros Signaling In Vascular Pathologymentioning

confidence: 99%

Targeted Interception of Signaling Reactive Oxygen Species in the Vascular Endothelium

Han

Shuvaev

Muzykantov

2012

Therapeutic Delivery

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are implicated as injurious and as signaling agents in human maladies including inflammation, hyperoxia, ischemia-reperfusion and acute lung injury. ROS produced by the endothelium play an important role in vascular pathology. They quench, for example, nitric oxide, and mediate pro-inflammatory signaling. Antioxidant interventions targeted for the vascular endothelium may help to control these mechanisms. Animal studies have demonstrated superiority of targeting ROS-quenching enzymes catalase and superoxide dismutase to endothelial cells over nontargeted formulations. A diverse arsenal of targeted antioxidant formulations devised in the last decade shows promising results for specific quenching of endothelial ROS. In addition to alleviation of toxic effects of excessive ROS, these targeted interventions suppress pro-inflammatory mechanisms, including endothelial cytokine activation and barrier disruption. These interventions may prove useful in experimental biomedicine and, perhaps, in translational medicine. Reactive oxygen species & vascular pathologyReactive oxygen species (ROS) superoxide anion (O 2 •− ) and hydrogen peroxide (H 2 O 2 ) are small molecules implicated as injurious and signaling agents in human maladies including inflammation, hyperoxia, ischemia-reperfusion (I/R) and acute lung injury (ALI) [1]. Activated phagocytes release ROS, causing tissue damage. Endothelial cells (ECs) lining the luminal surface of blood vessels also produce ROS [2] using the mitochondrial respiratory chain [3], membrane-bound NADPH oxidases (NOX) [4], xanthine oxidase [5], uncoupled nitric oxide synthase (NOS) [6] and other enzymatic systems ( Figure 1). The mitochondrial respiratory chain is the major producer of injurious ROS that play an important role in apoptosis and cell pathology [7]. ECs play key regulatory functions in the vascular system and, therefore, effects of endothelial ROS, both endogenous and exogenous, are of great biomedical importance [8].* Author for correspondence: Tel.: +1 215 898 9823, Fax: +1 215 573 2236, muzykant@mail.med.upenn.edu. Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.No writing assistance was utilized in the production of this manuscript. HHS Public AccessAuthor manuscript In order to control these effects of ROS in ECs (and, presumably, other cell types), at least two key intertwined aims must be achieved. First, we need to understand signaling and injurious mechanisms of ROS at a subcellular level. Second, we need means to interfere in these mechanisms at this level in selected cell types and phenotypes; for example, in the signaling endosomes of pathologically activated ECs. This article reviews these two aspects of targeted antioxidant interventions. ROS. This mechanism has been demonstrated for pro-inflammatory signaling induced ...

show abstract

“…However, these antioxidant interventions including delivery using membrane permeating peptides [25], provide no endothelial targeting and act in diverse tissue and cellular compartments [26]. Such spatially promiscuous effects may be beneficial in treatment generalized forms of oxidative stress and inflammation, such as sepsis and radiation injury, but insufficiently targeted for site-specific endothelial interventions.…”

Section: Reactive Oxygen Species (Ros) Antioxidant Defense and Spatimentioning

confidence: 99%

Targeted modulation of reactive oxygen species in the vascular endothelium

Shuvaev

Muzykantov

2011

Journal of Controlled Release

View full text Add to dashboard Cite

Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion or/and H2O2. These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS.

show abstract

Protein transduction of an antioxidant enzyme: subcellular localization of superoxide dismutase fusion protein in cells

Cited by 10 publications

References 23 publications

Neuroprotective Effects of 2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Against Oxidative Stress

Neuroprotective Effects of 2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Against Oxidative Stress

Targeted Interception of Signaling Reactive Oxygen Species in the Vascular Endothelium

Targeted modulation of reactive oxygen species in the vascular endothelium

Contact Info

Product

Resources

About