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81.
82.
Catherine Vigano Michel Julien Isabelle Carrier Philippe Gros Jean-Marie Ruysschaert 《The Journal of biological chemistry》2002,277(7):5008-5016
The dynamic changes occurring during the catalytic cycle of MDR3 P-glycoprotein (Pgp) and the role of each nucleotide-binding domain (NBD) in the transport process were investigated using attenuated total reflection Fourier transform infrared spectroscopy. For this purpose, wild-type Pgp and two mutations of homologous residues in each NBD were studied. On the one hand, we demonstrate here that, during its catalytic cycle, Pgp does not undergo secondary structure changes, but only modifications in its stability and accessibility to the external environment. On the other hand, amide H/D exchange kinetics demonstrate that homologous mutations in the two NBDs affect, in a different way, the dynamic properties of Pgp and also the dynamic changes occurring during ATP hydrolysis. These observations led to the conclusion that the NBDs have an asymmetric structure and different functions in the catalytic cycle of Pgp. Our data suggest that the release of drug from the membrane into the extracellular environment is due to decreased stability and/or increased accessibility to the external medium of the membrane-embedded drug-binding site(s). NBD1 would play an important role in this first restructuring of the membrane-embedded domains. NBD2 would be directly implicated in the subsequent restructuring of the membrane-embedded binding sites by which they recover their initial stability and accessibility to the membrane. It is proposed that this restructuring step would allow the binding and transport of another molecule of substrate. 相似文献
83.
Background Animals undergoing experimental manipulations, such as exposure to radiation, may exhibit physiologic and behavioral signs of pain and distress. Telemetry permits close monitoring of these parameters for early and effective management during procedures. Methods Radiotelemetric units were surgically implanted into 24 Macaca mulatta before 6.5‐Gy cobalt‐60 γ‐photon irradiation. Each unit transmitted electrocardiogram, intrathoracic pressure, and body temperature leads. Primate irradiation‐restraint boxes and housing cages were modified to collect telemetric signals before, during, and after irradiation. Results Differences in respiratory rate, heart rate, or body temperature in telemetric‐collected recordings, which were observed during non‐irradiation and irradiation sessions, were statistically insignificant. Conclusions Insignificant changes in the physiological parameters during monitoring suggest that the animals experienced no detectable pain or distress during irradiation. 相似文献
84.
Pyrimidine dimers in ultraviolet-irradiated DNA's 总被引:54,自引:0,他引:54
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86.
Bou Khalil M Chakrabandhu K Xu H Weerachatyanukul W Buhr M Berger T Carmona E Vuong N Kumarathasan P Wong PT Carrier D Tanphaichitr N 《Developmental biology》2006,290(1):220-235
Sperm gain full ability to bind to the zona(e) pellucida(e) (ZP) during capacitation. Since lipid rafts are implicated in cell adhesion, we determined whether capacitated sperm lipid rafts had affinity for the ZP. We demonstrated that lipid rafts, isolated as low-density detergent resistant membranes (DRMs), from capacitated pig sperm had ability to bind to homologous ZP. This binding was dependent on pig ZPB glycoprotein, a major participant in sperm binding. Capacitated sperm DRMs were also enriched in the male germ cell specific sulfogalactosylglycerolipid (SGG), which contributed to DRMs-ZP binding. Furthermore, SGG may participate in the formation of sperm DRMs due to its interaction with cholesterol, an integral component of lipid rafts, as shown by infrared spectroscopic studies. Since sperm capacitation is associated with cholesterol efflux from the sperm membrane, we questioned whether the formation of DRMs was compromised in capacitated sperm. Our studies indeed revealed that capacitation induced increased levels of sperm DRMs, with an enhanced ZP affinity. These results corroborated the implication of lipid rafts and SGG in cell adhesion and strongly suggested that the enhanced ZP binding ability of capacitated sperm may be attributed to increased levels and a greater ZP affinity of lipid rafts in the sperm plasma membrane. 相似文献
87.
Srivastava AS Kaushal S Mishra R Lane TA Carrier E 《Biochemical and biophysical research communications》2006,346(2):508-516
Differentiating embryonic stem (ES) cells are increasingly emerging as an important source of hematopoietic progenitors with a potential to be useful for both basic and clinical research applications. It has been suggested that dexamethasone facilitates differentiation of ES cells towards erythrocytes but the mechanism responsible for sequential expression of genes regulating this process are not well-understood. Therefore, we in vitro induced differentiation of murine ES cells towards erythropoiesis and studied the sequential expression of a set of genes during the process. We hypothesized that dexamethasone-activates its cognate nuclear receptors inducing up-regulation of erythropoietic genes such as GATA-1, Flk-1, Epo-R, and direct ES cells towards erythropoietic differentiation. ES cells were cultured in primary hematopoietic differentiation media containing methyl-cellulose, IMDM, IL-3, IL-6, and SCF to promote embryoid body (EB) formation. Total RNA of day 3, 5, and 9-old EBs was isolated for gene expression studies using RT-PCR. Cells from day 9 EBs were subjected to secondary differentiation using three different cytokines and growth factors combinations: (1) SCF, EPO, dexamethasone, and IGF; (2) SCF, IL-3, IL-6, and TPO; and, (3) SCF IL-3, IL-6, TPO, and EPO. Total RNA from day 12 of secondary differentiated ES cells was isolated to study the gene expression pattern during this process. Our results demonstrate an up-regulation of GATA-1, Flk-1, HoxB-4, Epo-R, and globin genes (alpha-globin, betaH-1 globin, beta-major globin, epsilon -globin, and zeta-globin) in the 9-day-old EBs, whereas, RNA from 5-day-old EBs showed expression of HoxB-4, epsilon-globin, gamma-globin, betaH1-globin, and Flk-1. Three-day-old EBs showed only HoxB-4 and Flk-1 gene expression and lacked expression of all globin genes. These findings indicate that erythropoiesis-specific genes are activated later in the course of differentiation. Gene expression studies on the ES cells of secondary EB origin cultured in media containing dexamethasone showed a down-regulation of GATA-3 and an up-regulation of GATA-1, Flk-1, and Epo-R in comparison to the two other cytokines and growth factor combinations containing media. The secondary differentiation also showed an enhanced production of erythrocytic precursors in dexamethasone containing media in comparison to that in the control media. Our results indicate that dexamethasone can prove to be an effective agent which can be employed to enhance differentiation towards erythrocytic progenitors from ES cells. 相似文献
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89.
Jessamyn S. Markley David R. Carrier 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2010,155(2):146-153
The highly derived mechanism birds use to ventilate their lungs relies on dorsoventral excursions of their heavily muscled sternum and abdominal viscera. Our expectation of the level of mechanical work involved in this mechanism led us to hypothesize that the metabolic cost of breathing is higher in birds than in other tetrapods. To test this theory, we used unidirectional artificial ventilation (UDV) to stop normal ventilatory movements in guinea fowl (Numida meleagris L.) at rest and during treadmill locomotion at three speeds. Oxygen consumption was measured during normal breathing and UDV, and the difference was used to approximate the cost of ventilation. Contrary to our prediction, metabolism increased when ventilatory movements ceased during UDV at rest. Although we do not understand why this occurred we suspect that UDV induced a homeostatic mechanism to counteract the loss of carbon dioxide. Nevertheless, across all running speeds, metabolism decreased significantly with UDV, indicating a minimum cost of ventilation during running of 1.43 ± 0.62% of total running metabolism or 0.48 ± 0.21 mL O2 (L ventilated)? 1. These results suggest that the metabolic cost of ventilation is low in birds and that it is within the range of costs reported previously for other amniotes. 相似文献
90.
In 2005, The American Physiological Society initiated The Living History of Physiology Project to recognize senior members who have made extraordinary contributions during their career to the advancement of the discipline and profession of physiology. Each Eminent Physiologist will be interviewed for archival purposes, and the video tape will be available from the American Physiological Society Headquarters. In addition, a biographical profile of the recipient will be published in Advances in Physiology Education. 相似文献