Effects of Intracellular Superoxide Removal at Acupoints with TAT-SOD on Obesity

Guo, Jingke; Chen, Yue; Yuan, Bin; Liu, Shutao; Rao, Pingfan

doi:10.1016/j.freeradbiomed.2011.09.036

Cited by 18 publications

(9 citation statements)

References 12 publications

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“…TAT-SOD in the cream is remarkably stable. SOD activity loss was less than 5.6% when TAT-SOD was stored at room temperature for 6 months [15]. …”

Section: Methodsmentioning

confidence: 99%

“…In our previous work, reproducible fluorescence lines superimposable to meridian lines were revealed on the frontal interior abdominal wall when intracellular ROS indicators were injected into living SD-rats tail vein, confirming the substantial implication of ROS in meridian system [14]. A controlled study has shown that topical application of superoxide dismutase (SOD) fused with the TAT peptide (TAT-SOD), to various acupoints along the meridian lines used in acupuncture to treat obesity, leads to significant weight loss [15], monitoring the effects of acupoint antioxidant intervention by measuring electrical potential difference along the meridian [16]. …”

Section: Introductionmentioning

confidence: 95%

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Topical Application of TAT‐Superoxide Dismutase in Acupoints LI 20 on Allergic Rhinitis

Guo

Zheng

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Reactive oxygen species are products of cellular metabolism and assigned important roles in biomedical science as deleterious factors in pathologies. In fact, some studies have shown that the therapeutic benefits of taking antioxidants were limited and the potential for therapeutic intervention remains unclear. New evidences showed that ROS have some ability of intercellular transportation. For treating allergic rhinitis, as a novel intracellular superoxide quencher, TAT-SOD applied to acupoints LI 20 instead of directly to nasal cavity can be used to test that. TTA group apply TAT-SOD cream prepared by adding purified TAT-SOD to the vehicle cream to acupoints LI 20, while placebo group used the vehicle cream instead. TTN group applied the same TAT-SOD cream directly to nasal cavity three times daily. Symptom scores were recorded at baseline and days 8 and 15. For the overall efficacy rate, TTA group was 81.0%, while placebo group was 5.9% and TTN was 0%. Malondialdehyde levels decreased observably in TTA group, and superoxide dismutase, catalase, and glutathione peroxidase levels remained basically unaffected. Enzymatic scavenging of the intracellular superoxide at acupoints LI 20 proved to be effective in treating allergic rhinitis, while no improvement was observed with the placebo group and TTN group.

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“…TAT-SOD in the cream is remarkably stable. SOD activity loss was less than 5.6% when TAT-SOD was stored at room temperature for 6 months [15]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Topical Application of TAT‐Superoxide Dismutase in Acupoints LI 20 on Allergic Rhinitis

Guo

Zheng

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…It has been used to deliver a wide variety of cargo into cells and has shown efficacy in preclinical models in vivo (38,59,60). In addition, several clinical trials are currently underway using TAT-mediated delivery (57,(60)(61)(62)(63)(64), although no therapy as of yet has received FDA approval, as issues associated with efficacy, bioavailablilty, and targeting remain primary challenges.…”

Section: Discussionmentioning

confidence: 99%

Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling

Kang¹,

Jung²,

Yin³

et al. 2017

Journal of Clinical Investigation

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ResultsA TAT-SNX9 peptide specifically blocks pSMAD3 nuclear import and profibrotic TGF-β signaling. We previously determined that SNX9 has an obligate role in mediating profibrotic TGF-β signaling dependent upon SMAD3 (24). In order to investigate colony formation, and cell migration; and (b) fibrotic changes associated with the bleomycin (BLM) and adenoviral models of lung fibrosis. Moreover, a 3-amino acid point mutant of the TAT-SNX9 peptide unable to bind pSMAD3 was ineffective in analogous in vitro and in vivo assays. Lysates from AKR-2B cells untreated (-) or stimulated (+) for 45 minutes with 5 ng/ml TGF-β were incubated with GST beads or the indicated fusion proteins immobilized on GST beads. Bound proteins were eluted and assessed by Western blot analysis for pSMAD3 or pSMAD2. Cell lysate reflects signal obtained from 10 μg total protein; the slower migrating band in the pSMAD3 lane is a nonspecific protein (right, representative of 3 separate experiments). (B) AKR-2B cells were transduced for 90 minutes with the indicated concentration of TAT peptide. Following washing and 1 hour TGF-β (5 ng/ml) treatment, nuclear fractions were isolated and assessed by Western blot analysis for pSMAD2, pSMAD3, or histone deacetylase 1 (HDAC) (left, representative of 3 separate experiments). Quantitation of nuclear pSMADs was performed with ImageJ software (NIH) and represents the mean ± SEM of 3 experiments (right). (C) Left panels: AKR-2B cells were incubated with vehicle (top panels) or transduced (bottom panels) as in B with TAT-SH3 or TAT-LC (1.8 μM). Following treatment with or without TGF-β (5 ng/ml) for 1 hour, immunofluorescence for SMAD3 or the HA-tagged TAT peptide was performed as described in Methods and nuclei were stained with DAPI. Upper and lower panels show 2 distinct microscopic fields for each condition. Original magnification in C: ×100. Right: quantitation of nuclear SMAD3 from 30 cells in each of 3 experiments. *P < 0.05; **P < 0.005; ***P < 0.0005, 1-way ANOVA followed by Dunnett's multiple comparisons test. The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 5 4 3 jci.orgVolume 127 Number 7 July 2017 sion of this fragment could act in trans as a dominant inhibitor of pSMAD3 nuclear uptake. To address this issue, constructs were prepared expressing either the SNX9 SH3 or LC domains fused to the cell-penetrating TAT peptide from HIV (39). Subsequent to TAT peptide transduction, cultures were treated with TGF-β and nuclear accumulation of pSMAD2 or pSMAD3 determined. As shown in Figure 1B and Supplemental Figure 2, while the TAT-SH3 peptide inhibited nuclear import of pSMAD3 in a dose-dependent manner and increased cytoplasmic pSMAD3, it had no effect on pSMAD2. Furthermore, consistent with the inability of the LC domain to bind receptorregulated SMADs (R-SMADs) ( Figure 1A), it was similarly ineffective in modulating nuclear translocation ( Figure 1B). These biochemical findings were independently confirmed using immunofluorescence ( Figure 1C and Supplemental Figure 3). While t...

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“…Enzymatic product was evaluated with the hydroxylamine hydrochloride method using superoxide generated by xanthine oxidase [ 18 , 19 ] and calculated using an improved formula [ 20 ]. In this experiment, one unit of enzymatic activity (1 U) was defined as the amount of SOD that inhibits 50% of superoxide radical.…”

Section: Methodsmentioning

confidence: 99%

Preparation and Characterization of Nanoparticles Made from Co-Incubation of SOD and Glucose

et al. 2017

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The attractive potential of natural superoxide dismutase (SOD) in the fields of medicine and functional food is limited by its short half-life in circulation and poor permeability across the cell membrane. The nanoparticle form of SOD might overcome these limitations. However, most preparative methods have disadvantages, such as complicated operation, a variety of reagents—some of them even highly toxic—and low encapsulation efficiency or low release rate. The aim of this study is to present a simple and green approach for the preparation of SOD nanoparticles (NPs) by means of co-incubation of Cu/Zn SOD with glucose. This method was designed to prepare nanoscale aggregates based on the possible inhibitory effect of Maillard reaction on heating-induced aggregation during the co-incubation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that the Maillard reaction occurred during the co-incubation process. It was found that enzymatically active NPs of Cu/Zn SOD were simultaneously generated during the reaction, with an average particle size of 175.86 ± 0.71 nm, and a Zeta potential of −17.27 ± 0.59 mV, as established by the measurement of enzymatic activity, observations using field emission scanning electron microscope, and analysis of dynamic light scattering, respectively. The preparative conditions for the SOD NPs were optimized by response surface design to increase SOD activity 20.43 fold. These SOD NPs showed storage stability for 25 days and better cell uptake efficacy than natural SOD. Therefore, these NPs of SOD are expected to be a potential drug candidate or functional food factor. To our knowledge, this is the first report on the preparation of nanoparticles possessing the bioactivity of the graft component protein, using the simple and green approach of co-incubation with glucose, which occurs frequently in the food industry during thermal processing.

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Effects of Intracellular Superoxide Removal at Acupoints with TAT-SOD on Obesity

Cited by 18 publications

References 12 publications

Topical Application of TAT‐Superoxide Dismutase in Acupoints LI 20 on Allergic Rhinitis

Topical Application of TAT‐Superoxide Dismutase in Acupoints LI 20 on Allergic Rhinitis

Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling

Preparation and Characterization of Nanoparticles Made from Co-Incubation of SOD and Glucose

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