• Title/Summary/Keyword: motor protein

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Yangkyuksanhwa-Tang Attenuates Ischemic Brain Injury in a Focal Photothrombosis Stroke Model (뇌허혈 마우스모델에서 양격산화탕이 뇌 손상 완화에 미치는 효과)

  • Han, Do-Kyung;Pak, Malk-Eun;Kwon, Ok-Sun;Choi, Byung-Tae
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1258-1266
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    • 2019
  • Yangkyuksanhwa-Tang (YKSH), consisting of nine different herbs, is commonly used in Soyangin-type individuals with stroke, based on the Sasang Constitution Theory in Korea. However, no evidence has yet confirmed a beneficial effect of YKSH in ischemic stroke treatment. In this study, we investigated the effects of YKSH on ischemic brain injury in a mouse model of cerebral ischemia. Focal cerebral ischemia in mice was induced by photothrombosis, and behavioral recovery was evaluated. Infarct volume, inflammation, and newly generated cells were evaluated by histology and immunochemistry. YKSH treatment resulted in a significant recovery from the motor impairments induced by focal cerebral ischemia, as determined with wire grip and rotarod tests. YKSH treatment also decreased the infarct volume and the number of cells positive for tumor necrosis factor-${\alpha}$ and myeloperoxidase when compared with a vehicle-treated control group. By contrast, YKSH treatment considerably increased the number of cells positive for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1, as well as the number of cells doubly positive for Ki67/doublecortin when compared with the vehicle-treated group. These results suggest that YKSH treatment attenuated the infarct size by anti-inflammatory action, astrocyte and microglia activation, and neuronal proliferation, thereby facilitating neurofunctional recovery from a cerebral ischemic assault. YKSH could therefore be a potential treatment for neurofunctional restoration of the injured brains of patients with stroke.

A Novel Pyrazolo[3,4-d]pyrimidine Induces Heme Oxygenase-1 and Exerts Anti-Inflammatory and Neuroprotective Effects

  • Lee, Ji Ae;Kwon, Young-Won;Kim, Hye Ri;Shin, Nari;Son, Hyo Jin;Cheong, Chan Seong;Kim, Dong Jin;Hwang, Onyou
    • Molecules and Cells
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    • v.45 no.3
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    • pp.134-147
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    • 2022
  • The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

Effects of Polychlorinated Biphenyls on the Expression of KAP3 Gene Involved in the 'Critical Period' of Rat Brain Sexual Differentiation

  • Lee, Chae-Kwan;Kang, Han-Seung;June, Bu-ll;Lee, Byung-Ju;Moon, Deog-Hwan;Kang, Sung-Goo
    • Animal cells and systems
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    • v.5 no.4
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    • pp.327-331
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    • 2001
  • There is a critical developmental period during which brain sexual differentiation proceeds irreversibly under the influence of gonadal hormone. Recently, kinesin superfamily-associated protein 3 (KAP3) gene expressed during the 'critical period' of rat brain differentiation was identified by us (Choi and Lee, 1999). KAP3 functions as a microtubule-based motor that transports membranous organelles anterogradely in cells, including neurons (Yamazaki et al., 1996). mRNA level of KAP3 gene markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited the prepubertal increase in KAP3 mRNA level (Choi and Lee, 1999). In the present study, we aimed to investigate the effects of polychlorinated biphenyls (PCBs), as endocrine disruptors (EDs) on the expression of KAP3 gene during the 'critical period' of rat brain development. In our data, PCBs significantly decreased the expression of KAP3 gene in the fetal (day 17) and the neonatal (day 6 after birth in) male and female rat brains. The body weight and the breeding ability were significantly decreased in the PCBs-exposed rats compared with the control. These results showed that PCBs affect the transcriptional level of brain sexual differentiation related gene, KAP3, in the fetal and the neonatal rat brains. The maternal exposure to the PCBs may lead to toxic response in embryonic brain sexual differentiation and breeding ability after sexual maturation. This study indicates that KAP3 gene may be useful as a gene marker to analyze the molecular mechanism of toxic response in the animal brain development and sexual maturation exposed to PCBs.

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Osteosarcopenic Obesity in Elderly: The Cascade of Bone, Muscle, and Fat in Inflammatory Process

  • Du, Yang;Oh, Chorong;No, Jae-kyung
    • Culinary science and hospitality research
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    • v.23 no.6
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    • pp.173-183
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    • 2017
  • Conditions related to body composition and aging, such as osteopenic obesity, sarcopenia/ sarcopenic obesity, and the newly termed osteosarcopenic obesity(triad of bone, muscle and adipose tissue impairment), are beginning to gain recognition. Currently, it has begun to attract the attention of scholars from all over the world, however, for this disease, it still needs a more clear understanding and perception. Therefore, this article considered the osteoporosis, muscle depression, and obesity, these diseases as a gate to study the relationship among muscle, bone, and fat. In addition, in the aging process, the formation of IGF-cortisol, testosterone, and estrogen is sensitive. These hormones can not only absorb muscle protein metabolism, but also affect alienation. The decrease in IGF-cortisol in the elderly resulted in increased visceral fat, decreased muscle mass and bone mineral density, and then affected decreased skeletal muscle atrophy and decreased quality. The reduction of skeletal muscle quality and strength and increase body fat affected the adipose tissue to produce inflammatory cytokines, thereby reduced skeletal muscle, promoted cardiovascular disease, metabolic syndrome and insulin resistance in chronic diseases. Almost all chronic inflammatory diseases were associated with bone, muscle and fat. These mechanisms were complex and interrelated. Inflammation reduces bone formation, increases fat and reduces muscle mass. And thus not only had a significant impact on the motor system, but also made the incidence increase of fracture, osteoporosis, fragile syndrome, fall, osteomalacia and other bone disease. This article aimed to start from the interaction between the muscles and bones of the elderly, extended to obesity, muscle deficiency, osteoporosis and other diseases, finally, from a nutritional point of view, to discuss how to treat osteoporosis obesity.

Facilitated Axonal Regeneration of Injured Sciatic Nerves by Yukmijihwang-tang Treatment

  • Kim, Jung-Hyun;Seol, In-Chan;Ryu, Ho-Ryong;Jo, Hyun-Kyung;An, Joung-Jo;Namgung, Uk;Kim, Yoon-Sik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.896-902
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    • 2008
  • Yukmijihwang-tang(YM) is used in Oriental medicine for treatments of diverse systemic symptoms including neurological dosorders. The present study was performed to examine potential effects of YM on growth-promoting activity of injured sciatic nerve axons. YM treatment in the injured sciatic nerve induced enhanced distal elongation of injured axons when measured 3 and 7 days after injury. Retrograde tracing of sciatic nerve axons showed YM-mediated increases in the number of DiI-labeled dorsal root ganglion (DRG) sensory neurons and spinal cord motor neurons at 3 days after injury. Hoechst nuclear staining showed that non-neuronal cell population was largely elevated by YM treatment in distal nerve area undergoing axonal regeneration. Furthermore, phospho-Erk1/2 protein levels were upregulated by YM treatment in the injured nerve area. These data suggest that YM may play a role in facilitated axonal regeneration in injured peripheral nerves. Further investigations of individual herbal components would be useful to explore effective molecular components and develop therapeutic strategies.

Neuroprotective Effect of Rapamycin (Autophagy Enhancer) in Transgenic SOD1-G93A Mice of Amyotrophic Lateral Sclerosis (근위축성측삭경화증의 SOD1-G93A 유전자 이식 마우스 모델에서 라파마이신의 신경보호효과)

  • Ahn, Suk-Won;Jeon, Gye Sun;Park, Kwang-Yeol;Hong, Yoon-Ho;Lee, Kwang-Woo;Sung, Jung-Joon
    • Annals of Clinical Neurophysiology
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    • v.15 no.2
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    • pp.53-58
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    • 2013
  • Background: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). Methods: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. Results: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. Conclusions: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.

Multitarget effects of Korean Red Ginseng in animal model of Parkinson's disease: antiapoptosis, antioxidant, antiinflammation, and maintenance of blood-brain barrier integrity

  • Choi, Jong Hee;Jang, Minhee;Nah, Seung-Yeol;Oh, Seikwan;Cho, Ik-Hyun
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.379-388
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    • 2018
  • Background: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. Methods: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/ kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. Results: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. Conclusion: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.

Effects of Electro-acupuncture and Therapeutic Exercise on Nervous system in the Ischemic Stroke Rats (전침자극과 운동치료가 허혈성 뇌졸중 백서모델의 신경계에 미치는 영향)

  • Yoo, Young-Dae;Kim, Gi-Do;Chun, Jin-Sung;Jeong, Hyun-Woo;Kim, Gye-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.1014-1020
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    • 2006
  • This study was intended to examine the effects of electroacupuncture(EA) and therapeutic exercise on the improvement of exercise function, BNDF, and HSP70 protein expression in an ischemic stroke model induced by MCA occlusion. Experiments were conducted for 1, 3 days, 1, 8 weeks respectively. Group I was a group of EA and therapeutic exercise; Group II was a group of therapeutic exercise; Group III was a group of EA; Group IV was a sham group of EA; Group V was a control group; and Group VI was a sham group without ischemic stroke. In each group, neurologic motor behavior test, histologic observations, BDNF, and HSP70 expression were observed and analyzed. The following results were obtained. The results of behavior test suggest that 8 weeks after ischemic stroke was induced, Group I improved in degeneration and inflammation of muscle fiber and decreased in destruction of nerve cells and cerebral infarction, indicating a similar state of muscle fiber and brain to Group VI. In immunohistochemical observations, Group I showed increase in BDNF and decrease in HSP70. Based on these results, EA and therapeutic exercise may improve muscle atrophy and change in BDNF and HSP70 expression of ischemic stroke rats and contribute to the improvement of exercise function.

The Restorative Effect of Gallic Acid on the Experimental Sciatic Nerve Damage Model

  • Gurkan, Gokhan;Erdogan, Mumin Alper;Yigitturk, Gurkan;Erbas, Oytun
    • Journal of Korean Neurosurgical Society
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    • v.64 no.6
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    • pp.873-881
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    • 2021
  • Objective : Peripheral nerve injuries occur mostly as a result of mechanical trauma. Due to the microvascular deterioration in peripheral nerve damage, it becomes challenging to remove free oxygen radicals. Gallic acid is a powerful antioxidant with anti-inflammatory effects and a free radical scavenger. The purpose of the study is to show that gallic acid contributes to the restorative effect in mechanical nerve damage, considering its antioxidant and anti-inflammatory effects. Methods : Thirty male Sprague Dawley albino mature rats were included in the study. Ten of them constituted the control group, 10 out of 20 rats for which sciatic nerve damage was caused, constituted the saline group, and 10 formed the gallic acid group. Post-treatment motor functions, histological, immunohistochemical, and biochemical parameters of the rats were evaluated. Results : Compared to the surgery+saline group, lower compound muscle action potential (CMAP) latency, higher CMAP amplitude, and higher inclined plane test values were found in the surgery+gallic acid group. Similarly, a higher nerve growth factor (NGF) percentage, a higher number of axons, and a lower percentage of fibrosis scores were observed in the surgery+gallic acid group. Finally, lower tissue malondialdehyde (MDA) and higher heat shock protein-70 (HSP-70) values were determined in the surgery+gallic acid group. Conclusion : Gallic acid positively affects peripheral nerve injury healing due to its anti-inflammatory and antioxidant effects. It has been thought that gallic acid can be used as a supportive treatment in peripheral nerve damage.

A novel HDAC6 inhibitor, CKD-504, is effective in treating preclinical models of huntington's disease

  • Endan Li;Jiwoo Choi;Hye-Ri Sim;Jiyeon Kim;Jae Hyun Jun;Jangbeen Kyung;Nina Ha;Semi Kim;Keun Ho Ryu;Seung Soo Chung;Hyun Sook Kim;Sungsu Lee;Wongi Seol;Jihwan Song
    • BMB Reports
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    • v.56 no.3
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    • pp.178-183
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    • 2023
  • Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.