Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model

Kim, Dae Won; Lee, Sung Ho; Ku, Sae Kwang; Cho, Soo Hyun; Cho, Sung‐Woo; Yoon, Ga Hyeon; Hwang, Hyun Sook; Park, Jinseu; Eum, Won Sik; Kwon, Oh Nam; Choi, Soo Young

doi:10.5483/bmbrep.2013.46.2.272

Cited by 22 publications

(15 citation statements)

References 35 publications

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“…To remove endotoxins of proteins, purified control PON1 and PEP-1-PON1 were treated with a Detoxi-Gel™ endotoxin removing gel (Pierce, Rockford, IL, USA) as per manufacturer’s instructions [34]. The Bradford assay was used to estimate protein concentration [37].…”

Section: Methodsmentioning

confidence: 99%

PEP-1-PON1 Protein Regulates Inflammatory Response in Raw 264.7 Macrophages and Ameliorates Inflammation in a TPA-Induced Animal Model

et al. 2014

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Paraoxonase 1 (PON1) is an antioxidant enzyme which plays a central role in various diseases. However, the mechanism and function of PON1 protein in inflammation are poorly understood. Since PON1 protein alone cannot be delivered into cells, we generated a cell permeable PEP-1-PON1 protein using protein transduction domains, and examined whether it can protect against cell death in lipopolysaccharide (LPS) or hydrogen peroxide (H2O2)-treated Raw 264.7 cells as well as mice with 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin inflammation. We demonstrated that PEP-1-PON1 protein transduced into Raw 264.7 cells and markedly protected against LPS or H2O2-induced cell death by inhibiting cellular reactive oxygen species (ROS) levels, the inflammatory mediator’s expression, activation of mitogen-activated protein kinases (MAPKs) and cellular apoptosis. Furthermore, topically applied PEP-1-PON1 protein ameliorates TPA-treated mice skin inflammation via a reduction of inflammatory response. Our results indicate that PEP-1-PON1 protein plays a key role in inflammation and oxidative stress in vitro and in vivo. Therefore, we suggest that PEP-1-PON1 protein may provide a potential protein therapy against oxidative stress and inflammation.

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Section: Methodsmentioning

confidence: 99%

PEP-1-PON1 Protein Regulates Inflammatory Response in Raw 264.7 Macrophages and Ameliorates Inflammation in a TPA-Induced Animal Model

et al. 2014

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“…Tat peptide is comprised of 9 amino acids (RKKRRQRRR), and it delivers proteins into cells and tissues such as brain cells (20)(21)(22). Several studies, including those undertaken by our group, have demonstrated that various Tat-fused proteins transduce into cells and protect against cell death in various diseases (23)(24)(25)(26)(27)(28)(29).…”

Section: Tat-atox1 Inhibits Streptozotocin-induced Cell Death In Pancmentioning

confidence: 99%

“…The recombinant Tat-ATOX1 plasmid was transformed into Escherichia coli BL21 (DE3; Novagen, Madison, WI, USA) and cultured in 0.5 mM isopropyl-β-D-thiogalactoside (IPTG; Duchefa, Haarlem, The Netherlands) at 18˚C overnight. The harvested cells were purified using an Ni 2+ -nitrilotriacetic acid Sepharose affinity column and PD-10 column chromatography (Amersham, Piscataway, NY, USA) (29,30). The concentration of purified protein was measured using the Bradford assay (Bio-Rad Laboratories, Hercules, CA, USA), as previously described (31).…”

Section: Purification Of Tat-atox1 Protein the Tat Expressionmentioning

confidence: 99%

Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model

Ahn

Kim

Shin

et al. 2016

International Journal of Molecular Medicine

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Antioxidant 1 (ATOX1) functions as an antioxidant against hydrogen peroxide and superoxide, and therefore may play a significant role in many human diseases, including diabetes mellitus (DM). In the present study, we examined the protective effects of Tat-ATOX1 protein on streptozotocin (STZ)-exposed pancreatic insulinoma cells (RINm5F) and in a mouse model of STZ-induced diabetes using western blot analysis, immunofluorescence staining and MTT assay, as well as histological and biochemical analysis. Purified Tat-ATOX1 protein was efficiently transduced into RINm5F cells in a dose- and time-dependent manner. Additionally, Tat-ATOX1 protein markedly inhibited reactive oxygen species (ROS) production, DNA damage and the activation of Akt and mitogen activated protein kinases (MAPKs) in STZ-exposed RINm5F cells. In addition, Tat-ATOX1 protein transduced into mice pancreatic tissues and significantly decreased blood glucose and hemoglobin A1c (HbA1c) levels as well as the body weight changes in a model of STZ-induced diabetes. These results indicate that transduced Tat-ATOX1 protein protects pancreatic β-cells by inhibiting STZ-induced cellular toxicity in vitro and in vivo. Based on these findings, we suggest that Tat-ATOX1 protein has potential applications as a therapeutic agent for oxidative stress-induced diseases including DM.

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“…After corneal application of liposome-compacted DNA, transgene expression is scarce and only detectable in the iris, limbus and conjunctiva (82). Internalization of drugs into the corneal epithelium can be achieved (83) as well as transfection of corneal cells with AVV with therapeutic transgenes (84), but gene delivery to the retina via the topical administration route is not currently effective.…”

Section: Delivery Strategies For Non-viral Gene Therapy In the Retinamentioning

confidence: 99%

Non-viral therapeutic approaches to ocular diseases: An overview and future directions

Zulliger

Conley

Naash

2015

Journal of Controlled Release

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Currently there are no viable treatment options for patients with debilitating inherited retinal degeneration. The vast variability in disease-inducing mutations and resulting phenotypes has hampered the development of therapeutic interventions. Gene therapy is a logical approach, and recent work has focused on ways to optimize vector design and packaging to promote optimized expression and phenotypic rescue after intraocular delivery. In this review, we discuss ongoing ocular clinical trials, which currently use viral gene delivery, but focus primarily on new advancements in optimizing the efficacy of non-viral gene delivery for ocular diseases. Non-viral delivery systems are highly customizable, allowing functionalization to improve cellular and nuclear uptake, bypassing cellular degradative machinery, and improving gene expression in the nucleus. Non-viral vectors often yield transgene expression levels lower than viral counterparts, however their favorable safety/immune profiles and large DNA capacity (critical for the delivery of large ocular disease genes) make their further development a research priority. Recent work on particle coating and vector engineering present exciting ways to overcome limitations of transient/low gene expression levels, but also highlight the fact that further refinements are needed before use in the clinic.

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Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model

Cited by 22 publications

References 35 publications

PEP-1-PON1 Protein Regulates Inflammatory Response in Raw 264.7 Macrophages and Ameliorates Inflammation in a TPA-Induced Animal Model

PEP-1-PON1 Protein Regulates Inflammatory Response in Raw 264.7 Macrophages and Ameliorates Inflammation in a TPA-Induced Animal Model

Tat-ATOX1 inhibits streptozotocin-induced cell death in pancreatic RINm5F cells and attenuates diabetes in a mouse model

Non-viral therapeutic approaches to ocular diseases: An overview and future directions

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