共查询到20条相似文献,搜索用时 15 毫秒
1.
Eun Jeong Sohn Dae Won Kim Mi Jin Kim Hoon Jae Jeong Min Jea Shin Eun Hee Ahn Soon Won Kwon Young Nam Kim Duk-Soo Kim Kyu Hyung Han Jinseu Park Hyun Sook Hwang Won Sik Eum Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
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. Thus, we examined the protective effects of MT-III proteins on oxidative stress-induced neuronal cell death and brain ischemic insult.Methods
A human MT-III gene was fused with a protein transduction domain, PEP-1 peptide, to construct a cell permeable PEP-1–MT-III protein. PEP-1–MT-III protein was purified using affinity chromatograph. Transduced PEP-1–MT-III proteins were detected by Western blotting and immunoflourescence. Cell viability and DNA fragmentation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium bromide (MTT) assay and terminal dexoynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Brain ischemic injury was detected with immunohistochemistry.Results
Purified PEP-1–MT-III proteins transduced into astrocytes in a time- and dose-dependent manner and protected against oxidative stress-induced cell death. Also, transduced PEP-1–MT-III proteins efficiently protected cells against DNA fragmentation. Furthermore, immunohistochemical analysis revealed that PEP-1–MT-III prevented neuronal cell death in the CA1 region of the hippocampus induced by transient forebrain ischemia. We demonstrated that transduced PEP-1–MT-III protein protects against oxidative stress induced cell death in vitro and in vivo.General significance
Transduced PEP-1–MT-III protein has neuroprotective roles as an antioxidant in vitro and in vivo. PEP-1–MT-III protein is a potential therapeutic agent for various human brain diseases such as stroke, Alzheimer's disease, and Parkinson's disease. 相似文献2.
Transduced human PEP-1-heat shock protein 27 efficiently protects against brain ischemic insult 总被引:1,自引:0,他引:1
An JJ Lee YP Kim SY Lee SH Lee MJ Jeong MS Kim DW Jang SH Yoo KY Won MH Kang TC Kwon OS Cho SW Lee KS Park J Eum WS Choi SY 《The FEBS journal》2008,275(6):1296-1308
Reactive oxygen species contribute to the development of various human diseases. Ischemia is characterized by both significant oxidative stress and characteristic changes in the antioxidant defense mechanism. Heat shock protein 27 (HSP27) has a potent ability to increase cell survival in response to oxidative stress. In the present study, we have investigated the protective effects of PEP-1-HSP27 against cell death and ischemic insults. When PEP-1-HSP27 fusion protein was added to the culture medium of astrocyte and primary neuronal cells, it rapidly entered the cells and protected them against cell death induced by oxidative stress. Immunohistochemical analysis revealed that, when PEP-1-HSP27 fusion protein was intraperitoneally injected into gerbils, it prevented neuronal cell death in the CA1 region of the hippocampus in response to transient forebrain ischemia. Our results demonstrate that transduced PEP-1-HSP27 protects against cell death in vitro and in vivo, and suggest that transduction of PEP-1-HSP27 fusion protein provides a potential strategy for therapeutic delivery in various human diseases in which reactive oxygen species are implicated, including stroke. 相似文献
3.
Seon Ae Eom Dae Won Kim Min Jea Shin Eun Hee Ahn Seok Young Chung Eun Jeong Sohn Hyo Sang Jo Su-Jeong Jeon Duk-Soo Kim Hyeok Yil Kwon Sung-Woo Cho Kyu Hyung Han Jinseu Park Won Sik Eum Soo Young Choi 《BMB reports》2015,48(7):395-400
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. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400] 相似文献
4.
Eun Hee Ahn Dae Won Kim Min Jea Shin Hye Ri Kim So Mi Kim Su Jung Woo Seon Ae Eom Hyo Sang Jo Duk-Soo Kim Sung-Woo Cho Jinseu Park Won Sik Eum Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
PEA-15 is abundantly expressed in both neurons and astrocytes throughout the brain. It is a multifunctional protein with the ability to increase cell survival via anti-apoptotic and anti-proliferative properties. However, the function of PEA-15 in neuronal diseases such as Parkinson's disease (PD) remains unclear. In this study, we investigated the protective effects of PEA-15 on neuronal damage induced by MPP+ in neuroblastoma SH-SY5Y and BV2 microglia cells and in a MPTP-induced PD mouse model using cell-permeable PEP-1-PEA-15.Methods
PEP-1-PEA-15 was purified using affinity chromatography. Cell viability and DNA fragmentation were examined by MTT assay and TUNEL staining. Dopaminergic neuronal cell death in the animal model was examined by immunohistochemistry.Results
PEP-1-PEA-15 transduced into the SH-SY5Y and BV2 cells in a time- and dose-dependent manner. Transduced PEP-1-PEA-15 protected against MPP+-induced toxicity by inhibiting intracellular ROS levels and DNA fragmentation. Further, it enhanced the expression levels of Bcl-2 and caspase-3 while reducing the expression levels of Bax and cleaved caspase-3. We found that PEP-1-PEA-15 transduced into the substantia nigra and prevented dopaminergic neuronal cell death in a MPTP-induced PD mouse. Also, we showed the neuroprotective effects in the model by demonstrating that treatment with PEP-1-PEA-15 ameliorated MPTP-induced behavioral dysfunctions and increased dopamine levels in the striatum.Conclusions
PEP-1-PEA-15 can efficiently transduce into cells and protects against neurotoxin-induced neuronal cell death in vitro and in vivo.General significance
These results demonstrate the potential for PEP-1-PEA-15 to provide a new strategy for protein therapy treatment of a variety of neurodegenerative diseases including PD. 相似文献5.
Sirtuin 2 (SIRT2), a member of the sirtuin family of proteins, plays an important role in cell survival. However, the biological function of SIRT2 protein is unclear with respect to inflammation and oxidative stress. In this study, we examined the protective effects of SIRT2 on inflammation and oxidative stress-induced cell damage using a cell permeative PEP-1–SIRT2 protein. Purified PEP-1–SIRT2 was transduced into RAW 264.7 cells in a time- and dose-dependent manner and protected against lipopolysaccharide- and hydrogen peroxide (H2O2)-induced cell death and cytotoxicity. Also, transduced PEP-1–SIRT2 significantly inhibited the expression of cytokines as well as the activation of NF-κB and mitogen-activated protein kinases (MAPKs). In addition, PEP-1–SIRT2 decreased cellular levels of reactive oxygen species (ROS) and of cleaved caspase-3, whereas it elevated the expression of antioxidant enzymes such as MnSOD, catalase, and glutathione peroxidase. Furthermore, topical application of PEP-1–SIRT2 to 12-O-tetradecanoylphorbol 13-acetate-treated mouse ears markedly inhibited expression levels of COX-2 and proinflammatory cytokines as well as the activation of NF-κB and MAPKs. These results demonstrate that PEP-1–SIRT2 inhibits inflammation and oxidative stress by reducing the levels of expression of cytokines and ROS, suggesting that PEP-1–SIRT2 may be a potential therapeutic agent for various disorders related to ROS, including skin inflammation. 相似文献
6.
Mi Jin Kim Hoon Jae Jeong Dae Won Kim Eun Jeong Sohn Hyo Sang Jo Duk-Soo Kim Hyun Ah Kim Eun Young Park Jong Hoon Park Ora Son Kyu Hyung Han Jinseu Park Won Sik Eum Soo Young Choi 《PloS one》2014,9(1)
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. 相似文献
7.
Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death 总被引:3,自引:0,他引:3
Choi SH Kim DW Kim SY An JJ Lee SH Choi HS Sohn EJ Hwang SI Won MH Kang TC Kwon HJ Kang JH Cho SW Park J Eum WS Choi SY 《Molecules and cells》2005,20(3):401-408
Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS. 相似文献
8.
Hoon Jae Jeong Dae Young Yoo Dae Won Kim Hyeon Ji Yeo Su Bin Cho Jiye Hyeon Jung Hwan Park Jinseu Park Won Sik Eum Hyun Sook Hwang Moo-Ho Won In Koo Hwang Soo Young Choi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Oxidative stress is a leading cause of various diseases, including ischemia and inflammation. Peroxiredoxin2 (PRX2) is one of six mammalian isoenzymes (PRX1–6) that can reduce hydrogen peroxide (H2O2) and organic hydroperoxides to water and alcohols.Methods
We produced PEP-1-PRX2 transduction domain (PTD)-fused protein and investigated the effect of PEP-1-PRX2 on oxidative stress-induced neuronal cell death by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blot, immunofluorescence microscopy, and immunohistochemical analysis.Results
Our data showed that PEP-1-PRX2, which can effectively transduce into various types of cells and brain tissues, could be implicated in suppressing generation of reactive oxygen species, preventing depolarization of the mitochondrial membrane, and inhibiting the apoptosis pathway in H2O2-stimulated HT22, murine hippocampal neuronal cells, likely resulting in protection of HT22 cells against H2O2-induced toxicity. In addition, we found that in a transient forebrain ischemia model, PEP-1-PRX2 inhibited the activation of astrocytes and microglia in the CA1 region of the hippocampus and lipid peroxidation and also prevented neuronal cell death against ischemic damage.Conclusions
These findings suggest that the transduced PEP-1-PRX2 has neuroprotective functions against oxidative stress-induced cell death in vitro and in vivo.General significance
PEP-1-PRX2 could be a potential therapeutic agent for oxidative stress-induced brain diseases such as ischemia. 相似文献9.
Jong Kyu Youn Dae Won Kim Seung Tae Kim Sung Yeon Park Eun Ji Yeo Yeon Joo Choi Hae-Ran Lee Duk-Soo Kim Sung-Woo Cho Kyu Hyung Han Jinseu Park Won Sik Eum Hyun Sook Hwang Soo Young Choi 《BMB reports》2014,47(10):569-574
Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and Fe2+, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson’s disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion (MPP+). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce MPP+-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD. [BMB Reports 2014; 47(10): 569-574] 相似文献
10.
Tat‐antioxidant 1 protects against stress‐induced hippocampal HT‐22 cells death and attenuate ischaemic insult in animal model
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So Mi Kim In Koo Hwang Dae Young Yoo Won Sik Eum Dae Won Kim Min Jea Shin Eun Hee Ahn Hyo Sang Jo Eun Ji Ryu Ji In Yong Sung‐Woo Cho Oh‐Shin Kwon Keun Wook Lee Yoon Shin Cho Kyu Hyung Han Jinseu Park Soo Young Choi 《Journal of cellular and molecular medicine》2015,19(6):1333-1345
Oxidative stress‐induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat‐Atox1 and examined the roles of Tat‐Atox1 in oxidative stress‐induced hippocampal HT‐22 cell death and an ischaemic injury animal model. Tat‐Atox1 effectively transduced into HT‐22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)‐induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat‐Atox1 regulated cellular survival signalling such as p53, Bad/Bcl‐2, Akt and mitogen‐activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat‐Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat‐Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat‐Atox1 protects against oxidative stress‐induced HT‐22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat‐Atox1 has potential as a therapeutic agent for the treatment of oxidative stress‐induced ischaemic damage. 相似文献
11.
Lee YP Kim DW Kang HW Hwang JH Jeong HJ Sohn EJ Kim MJ Ahn EH Shin MJ Kim DS Kang TC Kwon OS Cho SW Park J Eum WS Choi SY 《The FEBS journal》2012,279(11):1929-1942
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. Although the mechanism of PD remains unclear, oxidative stress is known to be important in its pathogenesis. This study investigated the protective effects of PEP-1-HSP27 on neuronal damage induced by 1-methyl-4-phenyl pyridinium (MPP(+) ) in SH-SY5Y cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-HSP27 rapidly entered the cells and protected them against MPP(+) -induced toxicity by inhibiting the reactive oxygen species levels and DNA fragmentation. Furthermore, transduced PEP-1-HSP27 prevented dopaminergic neuronal cell death in the substantia nigra of MPTP-induced PD mouse models. These results demonstrate that PEP-1-HSP27 provides a potential strategy for therapeutic delivery against various diseases and is a potential tool for the treatment of PD. 相似文献
12.
Methylglyoxal (MG), a metabolite of glucose, is the major precursor of protein glycation and induces apoptosis. MG is associated with neurodegeneration, including oxidative stress and impaired glucose metabolism, and is efficiently metabolized to S-D-lactoylglutathione by glyoxalase (GLO). Although GLO has been implicated as being crucial in various diseases including ischemia, its detailed functions remain unclear. Therefore, we investigated the protective effect of GLO (GLO1 and GLO2) in neuronal cells and an animal ischemia model using Tat-GLO proteins. Purified Tat-GLO protein efficiently transduced into HT-22 neuronal cells and protected cells against MG- and H2O2-induced cell death, DNA fragmentation, and activation of caspase-3 and mitogen-activated protein kinase. In addition, transduced Tat-GLO protein increased D-lactate in MG- and H2O2-treated cells whereas glycation end products (AGE) and MG levels were significantly reduced in the same cells. Gerbils treated with Tat-GLO proteins displayed delayed neuronal cell death in the CA1 region of the hippocampus compared with a control. Furthermore, the combined neuroprotective effects of Tat-GLO1 and Tat-GLO2 proteins against ischemic damage were significantly higher than those of each individual protein. Those results demonstrate that transduced Tat-GLO protein protects neuronal cells by inhibiting MG- and H2O2-mediated cytotoxicity in vitro and in vivo. Therefore, we suggest that Tat-GLO proteins could be useful as a therapeutic agent for various human diseases related to oxidative stress including brain diseases. 相似文献
13.
Dae Won Kim Hoon Jae Jeong Hye Won Kang Min Jea Shin Eun Jeong Sohn Mi Jin Kim Eun Hee Ahn Jae Jin An Sang Ho Jang Ki-Yeon Yoo Moo Ho Won Tae-Cheon Kang In Koo Hwang Oh-Shin Kwon Sung-Woo Cho Jinseu Park Won Sik Eum Soo Young Choi 《Free radical biology & medicine》2009,47(7):941-952
Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by reactive oxygen species (ROS). Ischemia is characterized by both oxidative stress and changes in the antioxidant defense system. Catalase (CAT) and superoxide dismutase (SOD) are major antioxidant enzymes by which cells counteract the deleterious effects of ROS. To investigate the protective effects of CAT, we constructed PEP-1–CAT cell-permeative expression vectors. When PEP-1–CAT fusion proteins were added to the culture medium of neuronal cells, they rapidly entered the cells and protected them against oxidative stress-induced neuronal cell death. Immunohistochemical analysis revealed that PEP-1–CAT prevented neuronal cell death in the hippocampus induced by transient forebrain ischemia. Moreover, we showed that the protective effect of PEP-1–CAT was observed in neuronal cells treated with PEP-1–SOD. Therefore, we suggest that transduced PEP-1–CAT and PEP-1–SOD fusion proteins could be useful as therapeutic agents for various human diseases related to oxidative stress, including stroke. 相似文献
14.
Kwon SW Sohn EJ Kim DW Jeong HJ Kim MJ Ahn EH Kim YN Dutta S Kim DS Park J Eum WS Hwang HS Choi SY 《Biochemical and biophysical research communications》2011,(2):354-359
Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe2+), 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 264.7 cells in time- and dose-dependent manners, and were stably maintained in the cells for about 60 h. In addition, fluorescence analysis revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into the cytoplasm of cells, while HO-1 proteins failed to be transduced. In lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins effectively inhibited the overexpression of pro-inflammatory mediators and cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can be used as a therapeutic molecule against reactive oxygen species-related inflammatory diseases. 相似文献
15.
Jung Hwan Park Dae Won Kim Min Jea Shin Jinseu Park Kyu Hyung Han Keun Wook Lee Jong Kook Park Yeon Joo Choi Hyeon Ji Yeo Eun Ji Yeo Eun Jeong Sohn Hyoung-Chun Kim EunJoo Shin Sung-Woo Cho Duk-Soo Kim Yong-Jun Cho Won Sik Eum Soo Young Choi 《BMB reports》2020,53(11):582
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. However, whether IDO-1 would inhibit hippocampal cell death is poorly known. Therefore, we explored the effects of cell permeable Tat-IDO-1 protein against oxidative stress-induced HT-22 cells and in a cerebral ischemia/reperfusion injury model. Transduced Tat-IDO-1 reduced cell death, ROS production, and DNA fragmentation and inhibited mitogen-activated protein kinases (MAPKs) activation in H2O2 exposed HT-22 cells. In the cerebral ischemia/reperfusion injury model, Tat-IDO-1 transduced into the brain and passing by means of the blood-brain barrier (BBB) significantly prevented hippocampal neuronal cell death. These results suggest that Tat-IDO-1 may present an alternative strategy to improve from the ischemic injury. 相似文献
16.
Jeong HJ Kim DW Woo SJ Kim HR Kim SM Jo HS Park M Kim DS Kwon OS Hwang IK Han KH Park J Eum WS Choi SY 《Molecules and cells》2012,33(5):471-478
Parkinson's disease (PD) is a well known neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays a critical role in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, the loss of function of which is linked to the autosomal recessive early onset of PD. Therefore, we investigated the protective effects of DJ-1 protein against SH-SY5Y cells and in a PD mouse model using a cell permeable Tat-DJ-1 protein. Tat-DJ-1 protein rapidly transduced into the cells and showed a protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reducing the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential therapeutic strategy for against ROS related human diseases including PD. 相似文献
17.
Parkinson's disease (PD) is a neurodegenerative disease characterized by a gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Ribosomal protein S3 (rpS3) has multiple functions related to protein synthesis, antioxidative activity, and UV endonuclease III activity. We have previously shown that PEP-1–rpS3 inhibits skin inflammation and provides neuroprotection against experimental cerebral ischemic damage. In this study, we examined whether PEP-1–rpS3 can protect DA neurons against oxidative stress in SH-SY5Y neuroblastoma cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1–rpS3 was efficiently delivered to SH-SY5Y cells and the SN of the brain as confirmed by Western blot and immunohistochemical analysis. PEP-1–rpS3 significantly inhibited reactive oxygen species generation and DNA fragmentation induced by 1-methyl-4-phenylpyridinium, consequently leading to the survival of SH-SY5Y cells. The neuroprotection was related to the antiapoptotic activity of PEP-1–rpS3 that affected the levels of proapoptotic and antiapoptotic mediators. In addition, immunohistochemical data collected using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that PEP-1–rpS3 markedly protected DA cells in the SN against MPTP-induced oxidative stress. Therefore, our results suggest that PEP-1–rpS3 may be a potential therapy for PD. 相似文献
18.
Choi HS An JJ Kim SY Lee SH Kim DW Yoo KY Won MH Kang TC Kwon HJ Kang JH Cho SW Kwon OS Park J Eum WS Choi SY 《Free radical biology & medicine》2006,41(7):1058-1068
Parkinson disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). However, the mechanism of the pathology of PD still remains poorly understood. Because the administration of the herbicide paraquat triggers selective dopaminergic neuronal cell death, exposure of mice to this herbicide is one valuable model for studying the pathological aspects of PD. In this study, we investigated the protective effects of PEP-1-SOD in vitro and in vivo under exposure to the herbicide paraquat. The viability of neuronal cells treated with paraquat was markedly increased by transduced PEP-1-SOD. When the PEP-1-SOD fusion protein was injected intraperitoneally into mice, a completely protective effect against dopaminergic neuronal cell death in the SN was observed. This protective effect was synergistically increased when the PEP-1-SOD was cotransduced with Tat-alpha-synuclein. These results suggest that PEP-1-SOD provides a strategy for therapeutic delivery in various human diseases related to reactive oxygen species, including PD. 相似文献
19.
Eun Hee Ahn Dae Won Kim Min Jea Shin Hyo Sang Jo Seon Ae Eom Duk-Soo Kim Eun Young Park Jong Hoon Park Sung-Woo Cho Jinseu Park Won Sik Eum Ora Son Hyun Sook Hwang Soo Young Choi 《BMB reports》2013,46(11):561-566
We examined the ways in which fenobam could promote not only the transduction of PEP-1-FK506BP into cells and tissues but also the neuroprotective effect of PEP-1-FK506BP against ischemic damage. Fenobam strongly enhanced the protective effect of PEP-1-FK506BP against H2O2-induced toxicity and DNA fragmentation in C6 cells. In addition, combinational treatment of fenobam with PEP-1-FK506BP significantly inhibited the activation of Akt and MAPK induced by H2O2, compared to treatment with PEP-1-FK506BP alone. Interestingly, our results showed that fenobam significantly increased the transduction of PEP-1-FK506BP into both C6 cells and the hippocampus of gerbil brains. Subsequently, a transient ischemic gerbil model study demonstrated that fenobam pretreatment led to the increased neuroprotection of PEP-1-FK506BP in the CA1 region of the hippocampus. Therefore, these results suggest that fenobam can be a useful agent to enhance the transduction of therapeutic PEP-1-fusion proteins into cells and tissues, thereby promoting their neuroprotective effects. [BMB Reports 2013; 46(11): 561-566] 相似文献
20.
Choi SH Kim SY An JJ Lee SH Kim DW Ryu HJ Lee NI Yeo SI Jang SH Won MH Kang TC Kwon HJ Cho SW Kim J Lee KS Park J Eum WS Choi SY 《FEBS letters》2006,580(30):6755-6762
The consequences of ultraviolet (UV) exposure are implicated in skin aging and cell death. The ribosomal protein S3 (rpS3) is one of the major proteins by which cells counteract the deleterious effects of UV and it plays a role in the repair of damaged DNA. In the present study, we investigated the protective effects of PEP-1-rpS3 fusion protein after UV-induced cell injury. A human rpS3 gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-rpS3 fusion protein. The expressed and purified fusion proteins were efficiently transduced into skin cells in a time- and dose-dependent manner. Once inside the cells, transduced PEP-1-rpS3 fusion protein was stable for 48 h. We showed that transduced PEP-1-rpS3 fusion protein increased cell viability and dramatically reduced DNA lesions in the UV exposed skin cells. Immunohistochemical analysis revealed that PEP-1-rpS3 fusion protein efficiently penetrated the epidermis as well as the dermis of the subcutaneous layer when sprayed on animal skin. These results suggest that PEP-1-rpS3 fusion protein can be used in protein therapy for various disorders related to UV, including skin aging and cancer. 相似文献