Tat-Thioredoxin-like protein 1 attenuates ischemic brain injury by regulation of MAPKs and apoptosis signaling.

Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein.

Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling.

Thioredoxin 1 (Trx1) serves a central role in redox homeostasis. It is involved in numerous other processes, including oxidative stress and apoptosis. However, to the best of our knowledge, the role of Trx1 in inflammation remains to be explored.

Utilization of an Intracellular Calcium Mobilization Assay for the Screening of Transduced FK506-Binding Proteins.

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Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury.

It is well known that oxidative stress participates in neuronal cell death caused production of reactive oxygen species (ROS). The increased ROS is a major contributor to the development of ischemic injury. Indoleamine 2,3-dioxygenase 1 (IDO-1) is involved in the kynurenine pathway in tryptophan metabolism and plays a role as an anti-oxidant.

Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling.

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on HO-induced HT-22 cell death and in an animal ischemia model were investigated.

PEP‑1‑glutaredoxin 1 protects against hippocampal neuronal cell damage from oxidative stress via regulation of MAPK and apoptotic signaling pathways.

Oxidative stress is known to be a primary risk factor for neuronal diseases. Glutaredoxin (GLRX)‑1, a redox‑regulator of the thioredoxin superfamily, is known to exhibit an important role in cell survival via various cellular functions. However, the precise roles of GLRX1 in brain ischemia are still not fully understood.

Tat-HSP22 inhibits oxidative stress-induced hippocampal neuronal cell death by regulation of the mitochondrial pathway.

Oxidative stress plays an important role in the progression of various neuronal diseases including ischemia. Heat shock protein 22 (HSP22) is known to protect cells against oxidative stress. However, the protective effects and mechanisms of HSP22 in hippocampal neuronal cells under oxidative stress remain unknown.

Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults.

Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia.

Tat-NOL3 protects against hippocampal neuronal cell death induced by oxidative stress through the regulation of apoptotic pathways.

Oxidative stress-induced apoptosis is associated with neuronal cell death and ischemia. The NOL3 [nucleolar protein 3 (apoptosis repressor with CARD domain)] protein protects against oxidative stress-induced cell death. However, the protective mechanism responsible for this effect as well as the effects of NOL3 against oxidative stress in ischemia remain unclear.

PEP-1-GSTpi protein enhanced hippocampal neuronal cell survival after oxidative damage.

Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein.

PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury.

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI).

Deer bone extract prevents against scopolamine-induced memory impairment in mice.

Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1-42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine.

Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger.

aged black garlic exerts anti-inflammatory effects by decreasing no and proinflammatory cytokine production with less cytoxicity in LPS-stimulated raw 264.7 macrophages and LPS-induced septicemia mice.

In this study, the anti-inflammatory and antisepticemic activities of a water extract of aged black garlic (AGE), which is not pungent, were compared with those of raw garlic extract (RGE). The methyl thiazolyl tetrazolium (MTT) assay showed that AGE was not toxic up to 1000 μg/mL and was at least four times less cytotoxic than RGE. AGE significantly suppressed the production of nitric oxide (NO), tumor-necrosis factor-α (TNF-α), and prostaglandin (PG)-E2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.

Tat-fused recombinant human SAG prevents dopaminergic neurodegeneration in a MPTP-induced Parkinson's disease model.

Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson's disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium (MPP(+)) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity.

PEP-1-PON1 protein regulates inflammatory response in raw 264.7 macrophages and ameliorates inflammation in a TPA-induced animal model.

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.

PEP-1-p18 prevents neuronal cell death by inhibiting oxidative stress and Bax expression.

P18, a member of the INK4 family of cyclin-dependent kinase inhibitors, is a tumor suppressor protein and plays a key cell survival role in a variety of human cancers. Under pathophysiological conditions, the INK4 group proteins participate in novel biological functions associated with neuronal diseases and oxidative stress. Parkinson's disease (PD) is characterized by loss of dopaminergic neurons, and oxidative stress is important in its pathogenesis.

Tat-Frataxin protects dopaminergic neuronal cells against MPTP-induced toxicity in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is caused by various factors such as reactive oxygen species (ROS), dysfunction of mitochondria, and aggregation of misfolded proteins, thereby leading to loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Frataxin (FXN) is associated with iron homeostasis and biogenesis of iron-sulfur clusters in the electron transport chain complex. In this study, we investigated the potential of Tat-FXN to cross the blood-brain barrier (BBB) and protect DA neurons against oxidative stress in a mouse model of PD.

PEP-1-metallothionein-III protein ameliorates the oxidative stress-induced neuronal cell death and brain ischemic insults.

Background: Oxidative stress is considered to be involved in a number of human diseases including ischemia. Metallothioneins (MT)-III can protect neuronal cells from the cytotoxicity of reactive oxygen species (ROS). However, MT-III proteins biological function is unclear in ischemia.

PEP-1-heat shock protein 27 protects from neuronal damage in cells and in a Parkinson's disease mouse model.

Heat shock proteins (HSPs) are a highly conserved family of proteins that are induced in response to various environmental stressors including reactive oxygen species. HSP27 is a chaperone protein with the ability to increase cell survival in response to oxidative stress. Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons.

Imipramine enhances neuroprotective effect of PEP-1-Catalase against ischemic neuronal damage.

The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes.

Anti-inflammatory effect of transduced PEP-1-cyclophilin A in Raw264.7 cells and 12-O-tetradecanoylphorbol-13-acetate-induced mice.

Aims: Cyclophilin A (CypA) is an immunophilin that acts as a receptor for the immunosuppressant drug cyclosporine A (CsA). CypA has emerged as a potential drug target for several inflammatory diseases, although the details of its mechanism are unclear. We examined the protective effects of CypA on inflammation in Raw 264.

Anti-inflammatory effect of transduced PEP-1-heme oxygenase-1 in Raw 264.7 cells and a mouse edema model.

Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe(2+)), is up-regulated by several cellular stress and cell injuries, including inflammation, ischemia and hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein transduction domain that is able to deliver exogenous molecules to living cells or tissues, would facilitate HO-1 delivery to target cells and tissues, and thereby effectively exert a therapeutically useful response against inflammation. Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were transduced into Raw 264.