共查询到20条相似文献,搜索用时 46 毫秒
1.
Kim W Kim DW Shin BN Yoo DY Nam SM Kim MJ Choi JH Yoon YS Won MH Choi SY Hwang IK 《Neurochemical research》2011,36(12):2452-2458
Frataxin plays important roles in the mitochondrial respiratory chain and in the differentiation of neurons during early development. In this study, we observed the effects of frataxin on cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus. For this, we constructed an expression vector, PEP-1, that was fused with frataxin to create a PEP-1-frataxin fusion protein that easily penetrated frataxin into the blood-brain barrier. Three mg/kg PEP-1-frataxin was intraperitoneally administered to mice once a day for 2 weeks. The administration of PEP-1 alone did not result in any significant changes in the number of Ki67-positive cells and doublecortin (DCX)-immunoreactive neuroblasts in the mouse dentate gyrus. However, the administration of PEP-1-frataxin significantly increased the number of Ki67-positive cells and DCX-immunoreactive neuroblasts in the mouse dentate gyrus. In addition, PEP-1-frataxin significantly reduced 4-hydroxynonenal protein levels and malondialdehyde formation, while Cu, Zn-superoxide dismutase protein levels were maintained. These results suggest that frataxin effectively increased cell proliferation and neuroblast differentiation by decreasing lipid peroxidation in the dentate gyrus. 相似文献
2.
Jung Hoon Choi Dae Won Kim Dae Young Yoo Hoon Jae Jeong Woosuk Kim Hyo Young Jung Sung Min Nam Jong Hwi Kim Yeo Sung Yoon Soo Young Choi In Koo Hwang 《Neurochemical research》2013,38(10):2046-2055
Oxidative stress initiates age-related reduction in hippocampal neurogenesis and the use of antioxidants has been proposed as an effective strategy to prevent or attenuate the reduction of neurogenesis in the hippocampus. In the present study, we investigated the effects of Cu,Zn-superoxide dismutase (SOD1) and/or peroxiredoxin-2 (PRX2) on cell proliferation and neuroblast differentiation in the dentate gyrus in a model of d-galactose-induced aging model. For this study, we constructed an expression vector, PEP-1, fused PEP-1 with SOD1 or PRX2, and generated PEP-1-SOD1 and PEP-1-PRX2 fusion protein. The aging model was induced by subcutaneous injection of d-galactose (100 mg/kg) to 6-week-old male mice for 10 weeks. PEP-1, PEP-1-SOD1 and/or PEP-1-PRX2 fusion protein was intraperitoneally administered to these mice at 13-week-old once a day for 3 weeks and sacrificed at 30 min after the last administrations. The administration of PEP-1-SOD1 and/or PEP-1-PRX2 significantly improved d-galactose-induced deficits on the escape latency, swimming speeds, platform crossings, spatial preference for the target quadrant in Morris water maze test. In addition, the administration of PEP-1-SOD1 and/or PEP-1-PRX2 ameliorated d-galactose-induced reductions of cell proliferation and neuroblast differentiation in the dentate gyrus and significantly reduced d-galactose-induced lipid peroxidation in the hippocampus. These effects were more prominent in the PEP-1-SOD1-treated group with PEP-1-PRX2. These results suggest that a SOD1 and/or PRX2 supplement to aged mice could improve the memory deficits, cell proliferation and neuroblast differentiation in the dentate gyrus of d-galactose induced aged mice by reducing lipid peroxidation. 相似文献
3.
Kim W Kim DW Yoo DY Chung JY Hwang IK Won MH Choi SY Jeon SW Jeong JH Hwang HS Moon SM 《Neurochemical research》2012,37(2):307-313
A rabbit model of spinal cord ischemia has been introduced as a good model to investigate the pathophysiology of ischemia-reperfusion (I-R)-induced paraplegia. In the present study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. For this study, the expression vector PEP-1 was constructed, and this vector was fused with SOD1 to create a PEP-1-SOD1 fusion protein that easily penetrated the blood-brain barrier. Spinal cord ischemia was induced by transient occlusion of the abdominal aorta for 15 min. PEP-1-SOD1 (0.5 mg/kg) was intraperitoneally administered to rabbits 30 min before ischemic surgery. The administration of PEP-1-SOD1 significantly improved neurological scores compared to those in the PEP-1 (vehicle)-treated ischemia group. Also, in this group, the number of cresyl violet-positive cells at 72 h after I-R was much higher than that in the vehicle-treated ischemia group. Malondialdehyde levels were significantly decreased in the ischemic spinal cord of the PEP-1-SOD1-treated ischemia group compared to those in the vehicle-treated ischemia group. In contrast, the administration of PEP-1-SOD1 significantly ameliorated the ischemia-induced reduction of SOD and catalase levels in the ischemic spinal cord. These results suggest that PEP-1-SOD1 protects neurons from spinal ischemic damage by decreasing lipid peroxidation and maintaining SOD and catalase levels in the ischemic rabbit spinal cord. 相似文献
4.
In Koo Hwang Sun Shin Yi Jae Hoon Shin Ki-Yeon Yoo Jung Hoon Choi Choong Hyun Lee Je Kyung Seong Yeo Sung Yoon Jeong Ho Park Moo-Ho Won 《Neurochemical research》2010,35(3):465-472
In the present study, we observed the effects of cyclosporine A (CsA), an efficient immunosuppressant, on cell proliferation
and neuroblast differentiation in the subgranular zone of the dentate gyrus (SZDG) in normal C57BL/6 mice using Ki67 and doublecortin
(DCX) immunohistochemical staining, respectively. At 8 weeks of age, vehicle (physiological saline) or CsA was daily administered
(40 mg/kg, i.p.) for 1 week. Animals were sacrificed at 2 weeks after last administration. CsA treatment did not show any
influences in neurons, astrocytes and microglia based on immunohistochemistry for its markers, respectively. However, in the
CsA-treated group, Fluoro-Jade B, a marker for neurodegeneration, positive cells were found in the SZDG, not in the vehicle-treated
group. In the vehicle-treated group, Ki67 immunoreactive (+) nuclei were clustered in the SZDG, whereas in the CsA-treated group Ki67+ nuclei were scattered in the SZDG, showing no difference in cell numbers. Numbers of DCX+ neuroblasts with well-developed processes (tertiary dendrites) were much lower in the CsA-treated group than those in the
vehicle-treated group; however, numbers of DCX+ neuroblasts with secondary dendrites were similar in both the groups. These results suggest that CsA significantly reduces
dendritic outgrowth and complexity from neuroblasts in the SZDG without any affecting in neurons, astrocytes and microglia
in normal mice. 相似文献
5.
Yoo DY Kim W Nam SM Yoo KY Lee CH Choi JH Won MH Hwang IK Yoon YS 《Neurochemical research》2011,36(12):2401-2408
We investigated the effects of a high-fat diet (HFD) and the subsequent treatment of metformin (met) and glimepiride (glim),
which are widely prescribed for type 2 diabetes, on cell proliferation and neuroblast differentiation using Ki67 and doublecortin
(DCX) immunohistochemistry, respectively. Animals were fed low-fat diet (LFD) or HFD for 8 weeks. After 5 weeks of the HFD
treatment, met alone or met + glim was administered orally once a day for 3 weeks. Body weight and food intake were much higher
in the HFD + vehicle-treated group than the LFD-treated group. The administration of met or met + glim to the HFD-treated
group resulted in a decrease in weight gain and food intake. Ki67-immunoreactive (+) nuclei, DCX+ neuroblasts and brain-derived neurotrophic factor (BDNF) protein levels were markedly decreased in the dentate gyrus (DG)
of the HFD + vehicle-treated group compared to the LFD-treated group. The administration of met or met + glim to the HFD-treated
group prevented the reduction of Ki67+ nuclei, DCX+ neuroblasts, BDNF levels in the DG. The intraventricular injection of K252a (a BDNF receptor blocker) to the HFD-treated
group treated met or met + glim distinctively lowered the reduction of cell proliferation and neuroblast differentiation induced
by HFD. These results suggest that a HFD significantly reduces cell proliferation and neuroblast differentiation by reducing
BDNF levels and these effects are ameliorated by treatment with met or met + glim. 相似文献
6.
Dae Young Yoo Dae Won Kim Jin Young Chung Hyo Young Jung Jong Whi Kim Yeo Sung Yoon In Koo Hwang Jung Hoon Choi Goang-Min Choi Soo Young Choi Seung Myung Moon 《Neurochemical research》2016,41(12):3300-3307
In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2?×?105) were administered intrathecally. In addition, PEP-1 or 0.5 mg/kg PEP-1-SOD1 was administered intraperitoneally to the Ad-MSC-treated rabbits. Motor behaviors and NeuN-immunoreactive neurons were significantly decreased in the vehicle-treated group after ischemia/reperfusion. Administration of Ad-MSCs significantly ameliorated the changes in motor behavior and NeuN-immunoreactive neuronal survival. In addition, the combination of PEP-1-SOD1 and Ad-MSCs further increased the ameliorative effects of Ad-MSCs in the spinal cord after ischemia. Furthermore, the administration of Ad-MSCs with PEP-1-SOD1 decreased lipid peroxidation and maintained levels of antioxidants such as SOD1 and glutathione peroxidase compared to the Ad-MSC alone group. These results suggest that combination therapy using Ad-MSCs and PEP-1-SOD1 strongly protects neurons from ischemic damage by modulating the balance of lipid peroxidation and antioxidants. 相似文献
7.
In Koo Hwang Il Yong Kim Eun Jung Joo Jae Hoon Shin Ji Won Choi Moo-Ho Won Yeo Sung Yoon Je Kyung Seong 《Neurochemical research》2010,35(4):645-650
In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes,
on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker
diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to
14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels
were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly
decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin
(DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in
the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG
compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation
and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and
neuroblast differentiation in the SZDG in diabetic rats. 相似文献
8.
Yoo DY Kim W Kim DW Yoo KY Chung JY Youn HY Yoon YS Choi SY Won MH Hwang IK 《Neurochemical research》2011,36(5):713-721
We investigated the effects of pyridoxine (vitamin B6) on cell death, cell proliferation, neuroblast differentiation, and the GABAergic system in the mouse dentate gyrus. We administered
pyridoxine (350 mg/kg intraperitoneally) to 8 week old mice twice a day for 14 days and sacrificed them at 10 weeks of age.
Pyridoxine treatment did not induce neuronal death or activate microglia in the dentate gyrus, while glial fibrillary acidic
protein (GFAP)-positive cells were significantly increased in the subgranular zone of the dentate gyrus. The increase in GFAP-positive
cells was confirmed to be due to proliferating cells based on double immunofluorescence staining. GFAP-positive cells, which
were also labeled with Ki67, a marker for cell proliferation, and doublecortin, a marker for neuroblast differentiation, were
significantly increased in the pyridoxine-treated group compared to those in the vehicle-treated group. Pyridoxine treatment
also increased the protein levels of glutamic acid decarboxylase (GAD) 67, an enzyme for GABA synthesis, and pyridoxal 5′-phosphate
(PNP) oxidase, an enzyme for pyridoxal phosphate synthesis, in the dentate gyrus. These results suggest that pyridoxine treatment
distinctly increases cell proliferation, neuroblast differentiation, and upregulated the GABAergic system, as revealed by
the increases of GAD67 and PNP oxidase in the mouse dentate gyrus. 相似文献
9.
Bai Hui Chen Bing Chun Yan Joon Ha Park Ji Hyeon Ahn Dae Hwan Lee In Hye Kim Jeong-Hwi Cho Jae-Chul Lee Sung Koo Kim Bonghee Lee Jun Hwi Cho Moo-Ho Won Yun Lyul Lee 《Neurochemical research》2013,38(9):1980-1988
Apripiprazole (APZ) is well known as an atypical antipsychotic and antidepressant. In the present study, we investigated effects of APZ on cell proliferation and neuronal differentiation in the dentate gyrus (DG) of the adolescent mouse using BruU, Ki-67 and doublecortin (DCX) immunohistochemistry. BruU, Ki-67 and DCX-positive (+) cells were easily detected in the subgranular zone of the DG in the vehicle- and APZ-treated group. We found that in the 8 mg/kg APZ-treated group numbers of Ki-67+, DCX+ and BrdU+/DCX+ cells were significantly increased compared with those in the vehicle-treated group. We also found that maturation and complexity of DCX+ dendrites in the 8 mg/kg APZ-treated group was well improved compared with those in the vehicle-treated group. In addition, markedly decreased lipid peroxidation and increased superoxide dismutase 2 (SOD2) level were observed in the DG of the 8 mg/kg APZ-treated group. Our present findings indicate that APZ can enhance cell proliferation and neuroblast differentiation, particularly maturation and complexity of neuroblast dendrites, in the DG via decreasing lipid peroxidation and increasing SOD2 level. 相似文献
10.
Yoo DY Choi JH Kim W Yoo KY Lee CH Yoon YS Won MH Hwang IK 《Neurochemical research》2011,36(2):250-257
Lemon balm, leaves of Melissa officinalis L., has been used for anti-anxiety and spasmolytics. We observed the extract of Melissa officinalis L. (MOE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of middle-aged mice (12 months
of age) using Ki67 and doublecortin (DCX), respectively. We also observed changes in corticosterone, GAD67 and GABA-transaminase
(GABA-T) to check their possible mechanisms related to neurogenesis. We administered 50 or 200 mg/kg MOE to the animals once
a day for 3 weeks. For labeling of newly generated cells, we also administered 5-bromodeoxyuridine (BrdU) twice a day for
3 days from the day of the first MOE treatment. Administration of 50 or 200 mg/kg MOE dose-dependently increased Ki67 positive
nuclei to 244.1 and 763.9% of the vehicle-treated group, respectively. In addition, 50 or 200 mg/kg MOE significantly increased
DCX positive neuroblasts with well-developed (tertiary) dendrites. Furthermore, MOE administration significantly increased
BrdU/calbindin D-28 k double labeled cells (integrated neurons into granule cells in the DG) to 245.2% of the vehicle-treated
group. On the other hand, administration of MOE reduced corticosterone levels in serum and decreased GABA-T levels in the
DG homogenates. These results suggest that MOE increases cell proliferation, neuroblast differentiation and integration into
granule cells by decreasing serum corticosterone levels as well as by increasing GABA levels in the mouse DG. 相似文献
11.
Bai Hui Chen Ji Hyeon Ahn Joon Ha Park Soo Young Choi Yun Lyul Lee Il Jun Kang In Koo Hwang Tae-Kyeong Lee Bich-Na Shin Jae-Chul Lee Seongkweon Hong Yong Hwan Jeon Myoung Cheol Shin Jun Hwi Cho Moo-Ho Won Young Joo Lee 《Neurochemical research》2018,43(3):600-608
It has been demonstrated that melatonin plays important roles in memory improvement and promotes neurogenesis in experimental animals. We examined effects of melatonin on cognitive deficits, neuronal damage, cell proliferation, neuroblast differentiation and neuronal maturation in the mouse dentate gyrus after cotreatment of scopolamine (anticholinergic agent) and melatonin. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected for 2 and/or 4 weeks to 8-week-old mice. Scopolamine treatment induced significant cognitive deficits 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly improved spatial learning and short-term memory impairments. Two and 4 weeks after scopolamine treatment, neurons were not damaged/dead in the dentate gyrus, in addition, no neuronal damage/death was shown after cotreatment of scopolamine and melatonin. Ki67 (a marker for cell proliferation)- and doublecortin (a marker for neuroblast differentiation)-positive cells were significantly decreased in the dentate gyrus 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly increased Ki67- and doublecortin-positive cells compared with scopolamine-treated group. However, double immunofluorescence for NeuN/BrdU, which indicates newly-generated mature neurons, did not show double-labeled cells (adult neurogenesis) in the dentate gyrus 2 and 4 weeks after cotreatment of scopolamine and melatonin. Our results suggest that melatonin treatment recovers scopolamine-induced spatial learning and short-term memory impairments and restores or increases scopolamine-induced decrease of cell proliferation and neuroblast differentiation, but does not lead to adult neurogenesis (maturation of neurons) in the mouse dentate gyrus following scopolamine treatment. 相似文献
12.
Yoo DY Kim W Kim IH Nam SM Chung JY Choi JH Yoon YS Won MH Hwang IK 《Neurochemical research》2012,37(1):223-231
We previously reported that sodium butyrate (SB), a histone deacetylase inhibitor, robustly increased pyridoxine-induced cell
proliferation and neuroblast differentiation in the dentate gyrus of the adult mouse. In this study, we investigated the effects
of treatment with SB combined with pyridoxine on cell proliferation and neuroblast differentiation in the dentate gyrus of
a mouse model of aging induced by d-galactose (d-gal). d-gal was administered to 20-week-old male mice (d-gal mice) for 10 weeks to induce changes that resemble natural aging in animals. Seven weeks after d-gal (100 mg/kg) treatment, vehicle (physiological saline; d-gal-vehicle mice) and SB (300 mg/kg) combined with pyridoxine (Pyr; 350 mg/kg) were administered to the mice (d-gal-Pyr-SB mice) for 3 weeks. Escape latency under water maze in the d-gal mice was longer than that in the control mice. In the d-gal-Pyr-SB mice, escape latency was similar to that in the control mice. In the d-gal mice, many cells in the granule cell layer of the dentate gyrus showed pyknosis and condensation of the cytoplasm. However,
in the d-gal-Pyr-SB mice, such cellular changes were rarely found. Furthermore, the d-gal mice showed a great reduction in cell proliferation (Ki67-positive cells) and neuroblast differentiation (doublecortin-positive
neuroblasts) in the dentate gyrus compared to control mice. However, in the d-gal-Pyr-SB mice, cell proliferation and neuroblast differentiation were markedly increased in the dentate gyrus. Furthermore,
the administration of pyridoxine with sodium butyrate significantly increased Ser133-phosphorylated cyclic AMP response element
binding protein in the dentate gyrus. These results indicate that the combination treatment of Pyr with SB in d-gal mice ameliorated the d-gal-induced reduction in cell proliferation, neuroblast differentiation, and memory deficits. 相似文献
13.
Yoo DY Woo YJ Kim W Nam SM Lee BH Yeun GH Yoon YS Won MH Park JH Hwang IK 《Neurochemistry international》2011,59(5):722-728
In this study, we synthesized [1-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-5-(1,2-dithiolan-3-yl)pentan-1-one, HBU-39], a (α)-lipoic acid derivative, and found this compound strongly inhibited butyrylcholinesterase (BuChE) in an in vitro experiment. We also examined the effects of HBU-39 on cell proliferation and neuroblast differentiation using the specific markers Ki67 and doublecortin (DCX), respectively, in the hippocampal dentate gyrus of a rat model of scopolamine-induced amnesia. For this, scopolamine was subcutaneously administered for 28 days by an ALzet osmotic minipump (44 mg/mL delivered at 2.5 μL/h). HBU-39 (1 mg/kg per day) and galantamine (an acetylcholinesterase inhibitor used as a control; 5 mg/kg per day) were intraperitoneally administered for 28 days. The administration of scopolamine significantly decreased the mean number of Ki67- and DCX-immunoreactive cells in the dentate gyrus. However, treatment with both HBU-39 and galantamine significantly ameliorated the reductions in cell proliferation and neuroblast differentiation. In particular, the mean number of Ki67- and DCX-immunoreactive cells was prominently abundant in the HBU-treated group compared to that in the galantamine-treated group. These results suggest that the BuChE inhibitor, HBU-39, can ameliorate the scopolamine-induced reductions of cell proliferation and neuroblast differentiation, and HBU-39 may be applicable to amnesia patients to promote memory functions. 相似文献
14.
You-en Zhang Jia-ning Wang Jun-ming Tang Ling-yun Guo Jian-ye Yang Yong-zhang Huang Yan Tan Shou-zhi Fu Xia Kong Fei Zheng 《Molecules and cells》2009,27(2):159-166
Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration
after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial
ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by
which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein
was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study,
we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis
revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced
into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-
SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function
of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine
kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically
active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases
related to SOD1 or to OFR. 相似文献
15.
Yoo DY Shin BN Kim IH Kim DW Yoo KY Kim W Lee CH Choi JH Yoon YS Choi SY Won MH Hwang IK 《Neurochemical research》2012,37(3):495-502
Sensitive to apoptosis gene (SAG) protein is a redox-inducible protein that protects cells against apoptosis induced by redox agents. In this study, we observed effects of SAG on cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus (DG) using Ki67 and doublecortin (DCX), respectively. For easy penetration into neurons, Tat-SAG expression vector was constructed by ligation with SAG and expression vector, Tat, in-frame with six histidine open-reading frames to generate the expression vector, and cloned into E. coli DH5α cells. One or 5?mg/kg Tat-SAG fusion protein (Tat-SAG) was intraperitoneally administered to mice once a day for 3?weeks. The administration of Tat-SAG significantly increased the number of 5-bromodeoxyuridine positive cells, Ki67 positive cells and DCX immunoreactive neuroblast in the mouse DG: Especially, in the 5?mg/kg Tat-SAG-treated mice, DCX positive neuroblasts showed a well-developed arborization of tertiary dendrites in the DG. On the other hand, we examined that the administration of Tat-SAG significantly reduced the DNA damage and lipid peroxidation judging from 8-hydroxy-2'-deoxyguanosine and 4-hydroxynonenal immunohistochemistry: The decrease was much more distinct in the 5?mg/kg Tat-SAG-treated mice than 1?mg/kg Tat-SAG-treated mice. This result suggests that SAG significantly increases cell proliferation, neuroblast differentiation and oxidative stress in normal states. 相似文献
16.
Copper chaperone for Cu,Zn-SOD supplement potentiates the Cu,Zn-SOD function of neuroprotective effects against ischemic neuronal damage in the gerbil hippocampus 总被引:13,自引:0,他引:13
Hwang IK Eum WS Yoo KY Cho JH Kim DW Choi SH Kang TC Kwon OS Kang JH Choi SY Won MH 《Free radical biology & medicine》2005,39(3):392-402
In the present study, we investigated the chronological alterations in SOD1 and its copper chaperone (chaperone for superoxide dismutase, CCS) immunoreactivities and their neuroprotective effects against neuronal damage in the gerbil hippocampus after 5 min of transient forebrain ischemia. SOD1 and CCS immunoreactivities were significantly increased in the stratum pyramidale of the CA1 region at 24 and 12 h after ischemic insult, respectively. At 24 h after ischemic insult, the SOD1 and CCS immunoreactivities were colocalized in the CA1 pyramidal cells of the stratum pyramidale. Thereafter, their immunoreactivities were significantly decreased in the CA1 region. To elucidate the effects of CCS or CCS/SOD1, we constructed the expression vectors PEP-1-SOD and PEP-1-CCS. In the CCS-treated group and the CCS/SOD1-treated group, 43.9 and 78.9% pyramidal cells, respectively, compared to the sham-operated group, were stained with cresyl violet 5 or 7 days after ischemic insult. The distribution pattern of active astrocytes and microglia in the PEP-CCS/SOD1-treated group 5 days after ischemic insult was similar to that of the sham-operated group. In addition, the SOD activity in the PEP-CCS- or PEP-CCS/SOD1-treated group was maintained by 10 days after ischemic insult. The SOD activity was higher in the PEP-CCS/SOD1-treated group vs the CCS-treated group. These results suggest that the enhanced expression of SOD1 and CCS may be related to compensatory mechanisms against ischemic damage and that cotreatment with CCS and SOD1 has a greater neuroprotective effect than treatment with CCS or SOD1 in isolation. 相似文献
17.
Dae Young Yoo Hyun Jung Kwon Kwon Young Lee Hyo Young Jung Jong Whi Kim Joon Ha Park 《Animal cells and systems.》2016,20(5):237-245
Transient forebrain ischemia promotes a robust increase in neuroblast differentiation in the hippocampal dentate gyrus that peaks 7–15 days after the surgery. In this study, we compared the glucose transporter 3 (GLUT3)-dependent glucose utilization and the dynamin-1 (DNM1)-dependent neurite growth in the hippocampus of Mongolian gerbils 15 days after the induction of transient forebrain ischemia. The animals were subjected to a 5 min transient ischemia protocol and sacrificed 15 days after the surgery. Both doublecortin (DCX) immunoreactive neuroblasts and DCX total protein levels were abundantly increased in the ischemic group compared to the levels observed in the control group. In addition, animals in the ischemic group showed elevated GLUT3 immunoreactivity in the subgranular zone of the dentate gyrus compared to animals in the control group. Based on the double immunofluorescent study, increased DCX-immunoreactive neuroblasts were co-localized with GLUT3-immunoreactive components in the dentate gyrus. However, both the immunoreactivity and the total protein levels of DNM1 were significantly decreased in the dentate gyrus and hippocampal CA1 regions of the ischemic group. These results suggest that the regeneration process such as neurite growth is lacking in the hippocampus 15 days after ischemia/reperfusion although neuroblasts production and glucose utilization increased in the hippocampus. 相似文献
18.
Spinal cord injury (SCI) produces excessive levels of reactive oxygen species (ROS) that induce apoptosis of neurons. Cu,Zn-superoxide dismutase (SOD1) is a key antioxidant enzyme that detoxifies intracellular ROS, thereby protecting cells from oxidative damage. PEP-1 is a peptide carrier capable of delivering full-length native peptides or proteins into cells. In the study described here, we fused a human SOD1 gene with PEP-1 in a bacterial expression vector to produce a genetic in-frame PEP-1-SOD1 fusion protein; we then investigated the neuroprotective effect of the fusion protein after SCI. The expressed and purified PEP-1-SOD1 was efficiently delivered into cultured cells and spinal cords in vivo, and the delivered fusion protein was biologically active. Systemic administration of PEP-1-SOD1 significantly decreased levels of ROS and protein carbonylation and nitration in spinal motor neurons after injury. PEP-1-SOD1 treatment also significantly inhibited mitochondrial cytochrome c release and activation of caspase-9 and caspase-3 in spinal cords after injury. Furthermore, PEP-1-SOD1 treatment significantly reduced ROS-induced apoptosis of motor neurons and improved functional recovery after SCI. These results suggest that PEP-1-SOD1 may provide a novel strategy for the therapeutic delivery of antioxidant enzymes that protect neurons from ROS after SCI. 相似文献
19.
Transduction of familial amyotrophic lateral sclerosis-related mutant PEP-1-SOD proteins into neuronal cells 总被引:1,自引:1,他引:0
An JJ Lee YP Kim SY Lee SH Kim DW Lee MJ Jeong MS Jang SH Kang JH Kwon HY Kang TC Won MH Cho SW Kwon OS Lee KS Park J Eum WS Choi SY 《Molecules and cells》2008,25(1):55-63
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective death of motor neurons. Mutations in the SOD1 gene are responsible for a familial form of ALS (FALS). Although many studies suggest that mutant SOD1 proteins are cytotoxic, the mechanism is not fully understood. To investigate the role of mutant SOD1 in FALS, human SOD1 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD fusion proteins (wild type and mutants). The expressed and purified PEP-1-SOD fusion proteins were efficiently transduced into neuronal cells. Neurones harboring the A4V, G93A, G85R, and D90A mutants of PEP-1-SOD were more vulnerable to oxidative stress induced by paraquat than those harboring wild-type proteins. Moreover, neurones harboring the mutant SOD proteins had lower heat shock protein (Hsp) expression levels than those harboring wild-type SOD. The effects of the transduced SOD1 fusion proteins may provide an explanation for the association of SOD1 with FALS, and Hsps could be candidate agents for the treatment of ALS. 相似文献
20.
Eum WS Kim DW Hwang IK Yoo KY Kang TC Jang SH Choi HS Choi SH Kim YH Kim SY Kwon HY Kang JH Kwon OS Cho SW Lee KS Park J Won MH Choi SY 《Free radical biology & medicine》2004,37(10):1656-1669
Reactive oxygen species (ROS) are implicated in reperfusion injury after transient focal cerebral ischemia. The antioxidant enzyme Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS after ischemia. Recently, we reported that denatured Tat-SOD fusion protein is transduced into cells and skin tissue. Moreover, PEP-1 peptide, which has 21 amino acid residues, is a known carrier peptide that delivers full-length native proteins in vitro and in vivo. In the present study, we investigated the protective effects of PEP-1-SOD fusion protein after ischemic insult. A human SOD gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-SOD fusion protein. The expressed and purified fusion proteins were efficiently transduced both in vitro and in vivo with a native protein structure. Immunohistochemical analysis revealed that PEP-1-SOD injected intraperitoneally (i.p.) into mice can have access into brain neurons. When i.p.-injected into gerbils, PEP-1-SOD fusion proteins prevented neuronal cell death in the hippocampus caused by transient forebrain ischemia. These results suggest that the biologically active intact forms of PEP-1-SOD provide a more efficient strategy for therapeutic delivery in various human diseases related to this antioxidant enzyme or to ROS, including stroke. 相似文献