排序方式: 共有12条查询结果,搜索用时 15 毫秒
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Kristi L. Norris Rui Hao Liang-Fu Chen Chun-Hsiang Lai Meghan Kapur Peter J. Shaughnessy Dennis Chou Jin Yan J. Paul Taylor Simone Engelender Anna E. West Kah-Leong Lim Tso-Pang Yao 《The Journal of biological chemistry》2015,290(22):13862-13874
Mutations in PARKIN (PARK2), an ubiquitin ligase, cause early onset Parkinson disease. Parkin was shown to bind, ubiquitinate, and target depolarized mitochondria for destruction by autophagy. This process, mitophagy, is considered crucial for maintaining mitochondrial integrity and suppressing Parkinsonism. Here, we report that under moderate mitochondrial stress, parkin does not translocate to mitochondria to induce mitophagy; rather, it stimulates mitochondrial connectivity. Mitochondrial stress-induced fusion requires PINK1 (PARK6), mitofusins, and parkin ubiquitin ligase activity. Upon exposure to mitochondrial toxins, parkin binds α-synuclein (PARK1), and in conjunction with the ubiquitin-conjugating enzyme Ubc13, stimulates K63-linked ubiquitination. Importantly, α-synuclein inactivation phenocopies parkin overexpression and suppresses stress-induced mitochondria fission, whereas Ubc13 inactivation abrogates parkin-dependent mitochondrial fusion. The convergence of parkin, PINK1, and α-synuclein on mitochondrial dynamics uncovers a common function of these PARK genes in the mitochondrial stress response and provides a potential physiological basis for the prevalence of α-synuclein pathology in Parkinson disease. 相似文献
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Effects of Mild Hypothermia on the Release of Regional Glutamate and Glycine During Extended Transient Focal Cerebral Ischemia in Rats 总被引:3,自引:0,他引:3
The present study is to determine the effect of mild hypothermia (MHT) on the release of glutamate and glycine in rats subjected to middle cerebral artery occlusion and reperfusion. The relationship between amino acid efflux and brain infarct volume was compared in different periods during MHT. Reversible middle cerebral artery occlusion was performed in Sprague-Dawley rats using a suture model. The rats were divided into four groups including (1) MHT during ischemia (MHTi), (2) MHT during reperfusion (MHTr), (3) MHT during ischemia and reperfusion (MHTi + r), and (4) a normothermic group (NT). Extracellular concentrations of glutamate and glycine in the cortex and striatum were monitored using in vivo microdialysis and analyzed using high-performance liquid chromatography. Morphometric measurements for infarct volume were performed using 2,3,5-triphenyltetrazolium chloride staining. The increase of glutamate and glycine in the ischemic cortex of the MHTi and MHTi + r rats during ischemic and reperfusion periods was significantly less than that of the NT rats (p < 0.05). However, there was no statistical difference among these groups in the peak of glutamate and glycine release in the striatum. Infarct volume paralleled the release of glutamate and glycine. The protective effect of MHTi and MHTi + r in reducing ischemia and reperfusion brain injury may be due to the attenuation of both glutamate and glycine release during ischemia and reperfusion. 相似文献
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Previously in the analgesic tail flick assay, mice and rats implanted with morphine pellets were shown to be highly tolerant to subcutaneously administered morphine but not to etorphine. The present purpose was to see whether the same differential response would be found to the antidiuretic response of morphine and etorphine in water-loaded rats because the presence of such a differential response would be of value in studying mechanisms of tolerance. Etorphine injected subcutaneously was about 1000x more potent than morphine in producing an antidiuretic response. Following chronic administration of morphine by pellet implantation, where the pellets remained in place during the drug challenge, profound tolerance developed to the antidiuretic effect of both morphine and etorphine. The dose-response curves for both were shifted to the right in non-parallel fashion with decreased slopes and antidiuretic efficacies. The large degree of tolerance developed to the antidiuretic effect of etorphine in morphine pellet implanted rats in contrast to the lack of development of tolerance to etorphine in the tail flick assay indicated that different mechanisms of development of tolerance exist for the two responses. 相似文献
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Tian-Xiao Li Bu-Lang Gao Dong-Yang Cai Zi-Liang Wang Liang-Fu Zhu Jiang-Yu Xue Wei-Xing Bai Ying-Kun He Li Li 《PloS one》2015,10(9)
Purpose
To investigate the safety and outcome of intracranial stenting for intracranial atherosclerotic stenosis (IAS).Materials and Methods
Between July 2007 and April 2013, 433 consecutive patients with IAS >70% underwent intracranial Wingspan stenting, and the data were prospectively analyzed.Results
Intracranial stenting was successful in 429 patients (99.1%), and the mean stenosis rate was improved from prestenting (82.3± 7.6)% to poststenting (16.6 ± 6.6)%. During the 30-day perioperative period, 29 patients (6.7%) developed stroke. The total perioperative stroke rate was significantly (P <0.01) higher in the basilar artery area than in others, whereas the hemorrhagic stroke rate was significantly (P <0.05) greater in the middle cerebral artery area than in others. The experience accumulation stage (13%) had a significantly (P <0.05) higher stroke rate than the technical maturation stage (4.8%). Clinical follow-up 6–69 months poststenting revealed ipsilateral stroke in 20 patients (5.5%). The one- and two-year cumulative stroke rates were 9.5% and 11.5%, respectively; the two-year cumulative stroke rate was significantly (P <0.05) greater in the experience accumulation stage (18.8%) than in the technical maturation stage (9.1%).Conclusion
Wingspan stenting for intracranial atherosclerotic stenosis is safe and the long-term stroke rate after stenting is low in a Chinese subpopulation. 相似文献9.
Choh Hao Li Liang-Fu Tseng Donald Yamashiro 《Biochemical and biophysical research communications》1978,85(2):795-800
The synthesis of βh-endorphin-(1–30) has been accomplished by the solid-phase procedure and its analgesic potency was assayed by the tail-flick method. Results showed that the synthetic analog had only 56% activity of the parent molecule. Thus, the complete sequence of 31 amino acid residues in βh-EP is required for full analgesic activity. 相似文献
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Fusion of cytotrophoblasts into the multinucleated syncytiotrophoblast layer is essential for the development of a functional placenta. The envelope protein of a human endogenous retrovirus W (HERV-W) family member, syncytin 1, has been shown to mediate placental cell fusion. Recently, the envelope protein of another HERV family member (HERV-FRD), syncytin 2, has been identified and shown to be highly expressed in the placenta. To better understand the biology of syncytin 2, in this study we first investigated syncytin 2 gene expression in normal and preeclamptic placentas and then characterized the functions of syncytin 2. The expression of syncytin 2 gene was decreased in preeclamptic placentas and could be stimulated by the cAMP stimulant forskolin. The endoprotease furin was found to be involved in the posttranslational cleavage of syncytin 1 and 2 polypeptides into surface and transmembrane subunits. In addition, proper association of the subunits of syncytins 1 and 2 is probably required for the functional integrity of each protein, because subunit swapping of syncytins 1 and 2 failed to generate fusogenic chimeras. Finally, we demonstrated that the disulfide bridge-forming CX(2)C and CX(7)C motifs found in syncytins 1 and 2 are essential for their fusogenic activities, because mutations in the CX(2)C motif not only abolished fusogenesis but also functioned as dominant-negative mutants. Our results suggest that syncytin 2 may function as a second fusogenic protein for placental cell fusion. 相似文献