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11.
Ligand binding and protein dynamics in neuroglobin 总被引:23,自引:0,他引:23
Kriegl JM Bhattacharyya AJ Nienhaus K Deng P Minkow O Nienhaus GU 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(12):7992-7997
Neuroglobin (Ngb) is a recently discovered protein in vertebrate brain tissue that belongs to the globin family of proteins. It has been implicated in the neuronal response to hypoxia or ischemia, although its physiological role has been hitherto unknown. Ngb is hexacoordinate in the ferrous deoxy form under physiological conditions. To bind exogenous ligands like O(2) and CO, the His E7 endogenous ligand is displaced from the sixth coordination. By using infrared spectroscopy and nanosecond time-resolved visible spectroscopy, we have investigated the ligand-binding reaction over a wide temperature range (3-353 K). Multiple, intrinsically heterogeneous distal heme pocket conformations exist in NgbCO. Photolysis at cryogenic temperatures creates a five-coordinate deoxy species with very low geminate-rebinding barriers. The photodissociated CO is observed to migrate within the distal heme pocket even at 20 K. Flash photolysis near physiological temperature (275-353 K) exhibits four sequential kinetic features: (i) geminate rebinding (t < 1 micros); (ii) extremely fast bimolecular exogenous ligand binding (10 micros < t < 1 ms) with a nontrivial temperature dependence; (iii) endogenous ligand binding (100 micros < t < 10 ms), which can be studied by using flash photolysis on deoxy Ngb; and (iv) displacement of the endogenous by the exogenous ligand (10 ms < t < 10 ks). All four processes are markedly nonexponential, suggesting that Ngb fluctuates among different conformations on surprisingly long time scales. 相似文献
12.
Apoptosis: a key in neurodegenerative disorders 总被引:1,自引:0,他引:1
Apoptosis is an important process in the development of the nervous system. Typically, approximately 50% of the neurons apoptose during neurogenesis before the nervous system matures. However, recent paradigms implicate premature apoptosis and/or aberrations in the fine control of neuronal apoptosis in the pathogenesis of a variety of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, stroke, brain trauma, spinal cord injury, and diabetic neuropathy. This review will focus on the current concepts salient to understanding the apoptosis death program, the mediators and control of cellular apoptosis, and the relationship between aberrant apoptosis and genesis of neurodegenerative disorders. The discussion will also highlight current advances in methodology, such as utilization of neuronal cell lines and mutant animal models, in investigations of neuronal apoptotic death. The knowledge of apoptosis mechanisms could underpin the basis for development of novel therapeutic strategies and treatment modalities that are directed at control of the neuronal apoptotic death program. 相似文献
13.
Khegai II Gulyaeva MA Popova NA Zakharova LA Ivanova LN 《Bulletin of experimental biology and medicine》2003,136(5):448-450
Morphofunctional immune disorders were revealed in vasopressin-deficient Brattleboro rats with diabetes insipidus during ontogeny. We observed a permanent decrease in the number of blood lymphocytes, increase in neutrophil count, reduced activity of macrophages, early involution of the thymus and spleen, and suppression of antibody production. These changes reflect impaired general resistance of these animals. 相似文献
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15.
Wladimir Wertelecki Lyubov Yevtushok Illia Kuznietsov Oleksandr Komov Serhii Lapchenko Diana Akhmedzanova Lyubov Ostapchuk 《European journal of medical genetics》2018,61(9):556-563
Pregnant women residing in areas impacted by the Chornobyl ionizing radiation of the Rivne Province in Ukraine have persistent higher levels of incorporated cesium-137. In these areas the neural tube defects and microcephaly rates are significantly higher than in areas with lower maternal cesium-137 incorporated levels. In two Rivne counties with populations proximal to nuclear power plants the rates of neural tube defects and microcephaly are the highest in the province. The neural tube defects rates in Rivne are persistently among the highest in Europe. 相似文献
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17.
Noninvasive differentiation of uric acid versus non-uric acid kidney stones using dual-energy CT 总被引:1,自引:0,他引:1
Primak AN Fletcher JG Vrtiska TJ Dzyubak OP Lieske JC Jackson ME Williams JC McCollough CH 《Academic radiology》2007,14(12):1441-1447
RATIONALE AND OBJECTIVES: To determine the accuracy and sensitivity for dual-energy computed tomography (DECT) discrimination of uric acid (UA) stones from other (non-UA) renal stones in a commercially implemented product. MATERIALS AND METHODS: Forty human renal stones comprising uric acid (n=16), hydroxyapatite (n=8), calcium oxalate (n=8), and cystine (n=8) were inserted in four porcine kidneys (10 each) and placed inside a 32-cm water tank anterior to a cadaver spine. Spiral dual-energy scans were obtained on a dual-source, 64-slice computed tomography (CT) system using a clinical protocol and automatic exposure control. Scanning was performed at two different collimations (0.6 mm and 1.2 mm) and within three phantom sizes (medium, large, and extra large) resulting in a total of six image datasets. These datasets were analyzed using the dual-energy software tool available on the CT system for both accuracy (number of stones correctly classified as either UA or non-UA) and sensitivity (for UA stones). Stone characterization was correlated with micro-CT. RESULTS: For the medium and large phantom sizes, the DECT technique demonstrated 100% accuracy (40/40), regardless of collimation. For the extra large phantom size and the 0.6-mm collimation (resulting in the noisiest dataset), three (two cystine and one small UA) stones could not be classified (93% accuracy and 94% sensitivity). For the extra large phantom size and the 1.2-mm collimation, the dual-energy tool failed to identify two small UA stones (95% accuracy and 88% sensitivity). CONCLUSIONS: In an anthropomorphic phantom model, dual-energy CT can accurately discriminate uric acid stones from other stone types. 相似文献
18.
S V Zaitsev L A Khegai B B Kim E M Gavrilova O G Yanovsky L A Zakharova 《Immunology letters》1992,32(1):27-30
The influence of Met-enkephalin on mitogenic stimulation of mouse splenocytes was investigated. Met-enkephalin (ME) was shown to suppress proliferation induced by Concanavalin A and activate proliferation induced by Staphylococcus enterotoxin A. Both effects were revealed at low (down to 10(-14) M) concentration of pentapeptide. Naloxone reversed ME influence on cell activation. The number of receptors for naloxone was shown to increase up to 2.5-fold during mitogenic activation. The difference in expression of various types of opioid receptors at mitogenic stimulation was demonstrated by ligand displacement experiments. 相似文献
19.
Neuronal apoptosis in neurodegeneration 总被引:3,自引:0,他引:3
Apoptosis mediates the precise and programmed natural death of neurons and is a physiologically important process in neurogenesis during maturation of the central nervous system. However, premature apoptosis and/or an aberration in apoptosis regulation is implicated in the pathogenesis of neurodegeneration, a multifaceted process that leads to various chronic disease states, such as Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) diseases, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and diabetic encephalopathy. The current review focuses on two major areas (a) the fundamentals of apoptosis, which includes elements of the apoptotic machinery, apoptosis inducers, and emerging concepts in apoptosis research, and (b) apoptotic involvement in neurodegenerative disorders, neuroprotective treatment strategies/modalities, and the mechanisms of, and signaling in, neuronal apoptosis. Current and new experimental models for apoptosis research in neurodegenerative diseases are also discussed. 相似文献
20.
Grazyna B Sadowska Xiaodi Chen Jiyong Zhang Yow-Pin Lim Erin E Cummings Oleksandr Makeyev Walter G Besio John Gaitanis James F Padbury William A Banks Barbara S Stonestreet 《Journal of cerebral blood flow and metabolism》2015,35(9):1388-1395
Pro-inflammatory cytokines contribute to hypoxic–ischemic brain injury. Blood–brain barrier (BBB) dysfunction represents an important component of hypoxic–ischemic brain injury in the fetus. Hypoxic–ischemic injury could accentuate systemic cytokine transfer across the fetal BBB. There has been considerable conjecture suggesting that systemic cytokines could cross the BBB during the perinatal period. Nonetheless, evidence to support this contention is sparse. We hypothesized that ischemia–reperfusion increases the transfer of systemic interleukin-1β (IL-1β) across the BBB in the fetus. Ovine fetuses at 127 days of gestation were studied 4 hours after 30 minutes of bilateral carotid artery occlusion and compared with a nonischemic group. Recombinant ovine IL-1β protein was expressed from an IL-1β pGEX-2 T vector in E. coli BL-21 cells and purified. The BBB function was quantified in 12 brain regions using a blood-to-brain transfer constant with intravenous 125I-radiolabeled IL-1β (125I-IL-1β). Interleukin-1β crossed the intact BBB in nonischemic fetuses. Blood-to-brain transport of 125I-IL-1β was higher (P<0.05) across brain regions in fetuses exposed to ischemia–reperfusion than nonischemic fetuses. We conclude that systemic IL-1β crosses the intact fetal BBB, and that ischemia–reperfusion increases transfer of this cytokine across the fetal BBB. Therefore, altered BBB function after hypoxia–ischemia facilitates entry of systemic cytokines into the brain of the fetus. 相似文献