Topical application of the antiapoptotic TAT-FNK protein prevents aminoglycoside-induced ototoxicity

Kashio, Akinori; Sakamoto, Takashi; Kakigi, Akinobu; Suzuki, Michitaka; Suzukawa, Keigo; Kondo, Kenji; Sato, Yoshitake; Asoh, Sadamitsu; Ohta, Shigeo; Yamasoba, Tatsuya

doi:10.1038/gt.2011.204

Cited by 8 publications

(2 citation statements)

References 52 publications

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“…The idea is to repair the protein-mediated diseases through the delivery of normal protein in vitro or in vivo. Some strategies have been used to manipulate cell functions by influencing signaling pathways. , For example, we can regulate the biomarkers of p53 and caspase to turn on/off the cell death for the diseases of apoptosis pathways. Delivering antigens to a specific site to stimulate a desired immune response has been explored .…”

Section: Introductionmentioning

confidence: 99%

A New Strategy for Intracellular Delivery of Enzyme Using Mesoporous Silica Nanoparticles: Superoxide Dismutase

et al. 2013

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We developed mesoporous silica nanoparticle (MSN) as a multifunctional vehicle for enzyme delivery. Enhanced transmembrane delivery of a superoxide dismutase (SOD) enzyme embedded in MSN was demonstrated. Conjugation of the cell-penetrating peptide derived from the human immunodeficiency virus 1 (HIV) transactivator protein (TAT) to mesoporous silica nanoparticle is shown to be an effective way to enhance transmembrane delivery of nanoparticles for intracellular and molecular therapy. Cu,Zn-superoxide dismutase (SOD) is a key antioxidant enzyme that detoxifies intracellular reactive oxygen species, ROS, thereby protecting cells from oxidative damage. In this study, we fused a human Cu,Zn-SOD gene with TAT in a bacterial expression vector to produce a genetic in-frame His-tagged TAT-SOD fusion protein. The His-tagged TAT-SOD fusion protein was expressed in E. coli using IPTG induction and purified using FMSN-Ni-NTA. The purified TAT-SOD was conjugated to FITC-MSN forming FMSN-TAT-SOD. The effectiveness of FMSN-TAT-SOD as an agent against ROS was investigated, which included the level of ROS and apoptosis after free radicals induction and functional recovery after ROS damage. Confocal microscopy on live unfixed cells and flow cytometry analysis showed characteristic nonendosomal distribution of FMSN-TAT-SOD. Results suggested that FMSN-TAT-SOD may provide a strategy for the therapeutic delivery of antioxidant enzymes that protect cells from ROS damage.

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Section: Introductionmentioning

confidence: 99%

A New Strategy for Intracellular Delivery of Enzyme Using Mesoporous Silica Nanoparticles: Superoxide Dismutase

et al. 2013

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“…[17]. Furthermore, Kashio et al reported that an artificial antiapoptotic protein, FNK, mediated with TAT peptide could enter the cochlea and effectively attenuate aminoglycoside-induced apoptosis of cochlear sensory hair cells in a guinea pig model [18]. More recently, Ookubo et al used poly-arginine (R11) to enhance transdermal delivery of several tyrosinase inhibitors on a guinea pig model and found the fusion protein efficiently penetrated through the SC and significantly inhibited UV-induced melanin synthesis [19].…”

Section: Introductionmentioning

confidence: 99%

Topical application of superoxide dismutase mediated by HIV-TAT peptide attenuates UVB-induced damages in human skin

Chen

Liu

Rao

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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The purpose of this study was to evaluate whether topical application of superoxide dismutase with cell penetrating peptide (HIV-TAT) could protect against skin damage induced by UVB irradiation in humans. The permeability through stratum corneum of large proteins linked to TAT peptide was firstly confirmed by confocal microscopy and tape stripping. Ten healthy volunteers with either Fitzpatrick skin type II or III were recruited in this clinical study. TAT-SOD (300units/cm(2)) and vehicle cream were applied on two symmetric areas of both inner upper arms 1h prior to UVB irradiation. After one hour of pretreatment, subjects received 10 incremental doses of UVB on pretreated areas. 24h later, erythema, blood flow and apoptotic cells were measured. Pretreatment with TAT-SOD 1h prior to UVB radiation promoted a mean minimal erythema dose (MED) increase of 36.6±18.4% (p=0.013<0.05. n=10) compared to vehicle control. The median blood flow values of all subjects following 2 and 3-MED of UVB were 107.8±51.0units and 239.5±88.0units respectively, which account for 26% and 25% decrease with respect to vehicle groups. These data suggest that TAT-SOD significantly suppresses UVB induced erythema formation and blood flow rise. Furthermore, pretreatment with TAT-SOD 1h prior to 2-MED of UVB irradiation reduced the apoptotic sunburn cell formation by 47.6±8.6% (p<0.0001) in all subjects. Evaluating results generated from all measurements, we conclude that topical application of TAT-SOD significantly attenuates UVB-induced skin damage in man. These biological effects of TAT-SOD are probably mediated via its free radical scavenging properties, clearly differentiating it from other physical sunscreen agents.

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Molecular basis of hair cell loss

Furness

2015

Cell Tissue Res

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Mechanisms that lead to the death of hair cells are reviewed. Exposure to noise, the use of ototoxic drugs that damage the cochlea and old age are accompanied by hair cell death. Outer hair cells are often more susceptible than inner hair cells, partly because of an intrinsically greater susceptibility; high frequency cells are also more vulnerable. A common factor in hair cell loss following age-related changes and exposure to ototoxic drugs or high noise levels is the generation of reactive oxygen species, which can trigger intrinsic apoptosis (the mitochondrial pathway). However, hair cell death is sometimes produced via an extracellular signal pathway triggering extrinsic apoptosis. Necrosis and necroptosis also play a role and, in various situations in which cochlear damage occurs, a balance exists between these possible routes of cell death, with no one mechanism being exclusively activated. Finally, the numerous studies on these mechanisms of hair cell death have led to the identification of many potential therapeutic agents, some of which have been used to attempt to treat people exposed to damaging events, although clinical trials are not yet conclusive. Continued work in this area is likely to lead to clinical treatments that could be used to prevent or ameliorate hearing loss.

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Topical application of the antiapoptotic TAT-FNK protein prevents aminoglycoside-induced ototoxicity

Cited by 8 publications

References 52 publications

A New Strategy for Intracellular Delivery of Enzyme Using Mesoporous Silica Nanoparticles: Superoxide Dismutase

A New Strategy for Intracellular Delivery of Enzyme Using Mesoporous Silica Nanoparticles: Superoxide Dismutase

Topical application of superoxide dismutase mediated by HIV-TAT peptide attenuates UVB-induced damages in human skin

Molecular basis of hair cell loss

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