排序方式: 共有28条查询结果,搜索用时 15 毫秒
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Qin Gu Lijing Zhai Xing Feng Jing Chen Zhigang Miao Liyan Ren Xuanchen Qian Jian Yu Yan Li Xingshun Xu Chun-Feng Liu 《Neurochemistry international》2013
Apelin is an endogenous ligand of G protein-coupled receptor-apelin and angiotensin-1-like receptor (APJ). The biological effects of apelin–APJ system are reported in multiple systems including cardiovascular, endocrinal, and gastrointestinal system. Previous studies had shown that apelin-13 is a potential protective agent on cardiac ischemia; however, the role of apelin in the central nervous system remained unknown. In this study, we investigated therapeutic effects of apelin-36, a long form of apelin, in ischemic brain injury models. We found that apelin-36 reduced cerebral infarct volume in the middle cerebral artery occlusion (MCAO) model and the neonatal hypoxic/ischemic (H/I) injury model. Apelin-36 improved neurological deficits in the MCAO model and promoted long-term functional recovery after H/I brain injury. We further explored the protective mechanisms of apelin-36 on H/I brain injury. We clearly demonstrated that apelin-36 significantly reduced the levels of cleaved caspase-3 and Bax, two well-established apoptotic markers after H/I injury, indicating the anti-apoptotic activity of apelin-36 in ischemic injury. Since apelin-36 increased the level of phosphorylated Akt after H/I injury, we treated neonates with a specific PI3K inhibitor LY294002. We found that LY294002 decreased the phosphorylated Akt level and attenuated protective effects of apelin-36 on apoptosis. These suggested that the PI3K/Akt pathway was at least in part involved in the anti-apoptotic mechanisms of apelin-36. Our findings demonstrated that apelin-36 was a promising therapeutic agent on the treatment of ischemic brain injury. 相似文献
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Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells 总被引:3,自引:0,他引:3
Xu X Chua CC Kong J Kostrzewa RM Kumaraguru U Hamdy RC Chua BH 《Journal of neurochemistry》2007,103(5):2004-2014
Glutamate, a major excitatory neurotransmitter in the CNS, plays a critical role in neurological disorders such as stroke and Parkinson's disease. Recent studies have suggested that glutamate excess can result in a form of cell death called glutamate-induced oxytosis. In this study, we explore the protective effects of necrostatin-1 (Nec-1), an inhibitor of necroptosis, on glutamate-induced oxytosis. We show that Nec-1 inhibits glutamate-induced oxytosis in HT-22 cells through a mechanism that involves an increase in cellular glutathione (GSH) levels as well as a reduction in reactive oxygen species production. However, Nec-1 had no protective effect on free radical-induced cell death caused by hydrogen peroxide or menadione, which suggests that Nec-1 has no antioxidant effects. Interestingly, the protective effect of Nec-1 was still observed when cellular GSH was depleted by buthionine sulfoximine, a specific and irreversible inhibitor of glutamylcysteine synthetase. Our study further demonstrates that Nec-1 significantly blocks the nuclear translocation of apoptosis-inducing factor (a marker of caspase-independent programmed cell death ) and inhibits the integration of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (a pro-death member of the Bcl-2 family) into the mitochondrial membrane. Taken together, these results demonstrate for the first time that Nec-1 prevents glutamate-induced oxytosis in HT-22 cells through GSH related as well as apoptosis-inducing factor and Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-related pathways. 相似文献
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Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression and to develop novel therapeutic strategies. Our previous studies showed that Abelson helper integration site-1 (Ahi1) deficiency causes depression-like behaviors in mice. In this study, we characterized the biochemical and behavioral changes in Ahi1 knockout (KO) mice. In Ahi1 KO mice, neurotransmitters including serotonin and dopamine were significantly decreased in different brain regions. However, glutamate and GABA levels were not affected by Ahi1 deficiency. The antidepressant imipramine attenuated depressive behaviors and partially restored brain serotonin level in Ahi1 KO mice. Our findings suggest that Ahi1 KO mice can be used for studying the mechanisms of depression and screening therapeutic targets. 相似文献
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Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice 下载免费PDF全文
Yamin Wang Bin Wang Jiaqi Lu Haixia Shi Siyi Gong Yufan Wang Ronald C. Hamdy Balvin H. L. Chua Lingli Yang Xingshun Xu 《Journal of neurochemistry》2017,143(5):561-568
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Gang Du Hui Tu Xiaojing Li Aijie Pei Jing Chen Zhigang Miao Jizhen Li Chen Wang Hong Xie Xingshun Xu Heqing Zhao 《Neurochemical research》2014,39(2):269-275
Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke. 相似文献
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Yunzhu Qian Yingying Zhang Bin Wei Mengshu Zhang Jianxin Yang Cuihua Leng Zili Ge Xingshun Xu Miao Sun 《Journal of genetics》2018,97(1):137-143
Cleidocranial dysplasia (CCD; OMIM: 119600) is a rare autosomal dominant skeletal dysplasia caused by RUNX2 gene mutations. The present study described a sporadic case with CCD. The clinical data of the proband with CCD was reported and genetic analysis was performed. The proband presented with typical CCD features including supernumerary impacted teeth, bilateral clavicle dysplasia, delayed closure of cranial sutures, and short stature; while his hands were normal. Sequencing analysis of the entire coding region of the RUNX2 gene revealed no pathogenic changes; however, copy-number analysis with the Affymetrix HD array found \(\sim \)500 kb genomic microdeletion. Real-time quantitative PCR validated this microdeletion in the 1–4 exons of the RUNX2 gene. The junction point of the breaking DNA was located in the directly oriented AluSz6 and AluSx repetitive elements, indicating that this microdeletion might be generated through an Alu–Alu mediated mechanism. In addition, this microdeletion existed in 21.8% of the asymptomatic mother’s peripheral blood cells, demonstrating that the mosaicism was not associated with CCD phenotypes. In summary, a pathogenic microdeletion in the RUNX2 gene located on chromosome 6 was responsible for CCD. 相似文献
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Yandong Zhang Jin You Xingshun Wang Jason Weber 《Molecular and cellular biology》2015,35(17):2918-2931
DEAD/DEAH box RNA helicases play essential roles in numerous RNA metabolic processes, such as mRNA translation, pre-mRNA splicing, ribosome biogenesis, and double-stranded RNA sensing. Herein we show that a recently characterized DEAD/DEAH box RNA helicase, DHX33, promotes mRNA translation initiation. We isolated intact DHX33 protein/RNA complexes in cells and identified several ribosomal proteins, translation factors, and mRNAs. Reduction of DHX33 protein levels markedly reduced polyribosome formation and caused the global inhibition of mRNA translation that was rescued with wild-type DHX33 but not helicase-defective DHX33. Moreover, we observed an accumulation of mRNA complexes with the 80S ribosome in the absence of functional DHX33, consistent with a stalling in initiation, and DHX33 more preferentially promoted structured mRNA translation. We conclude that DHX33 functions to promote elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Our results reveal a newly recognized function of DHX33 in mRNA translation initiation, further solidifying its central role in promoting cell growth and proliferation. 相似文献