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1.
The assignment of carbon monoxide association rate constants to the alpha and beta subunits in native and mutant human deoxyhemoglobin tetramers 总被引:2,自引:0,他引:2
A J Mathews J S Olson J P Renaud J Tame K Nagai 《The Journal of biological chemistry》1991,266(32):21631-21639
The association kinetics of CO binding to site-directed mutants of human deoxyhemoglobin were measured by stopped-flow rapid mixing techniques at pH 7.0, 20 degrees C. Hemoglobin tetramers were constructed from one set of native subunits and one set of mutated partners containing His(E7) to Gly, Val(E11) to Ala, or Val(E11) to Ile substitutions. The reactivity of beta Cys93 with p-hydroxymercuribenzoate was measured to ensure that the mutant deoxyhemoglobins were capable of forming T-state quaternary conformations. Time courses for the complete binding of CO were measured by mixing the deoxygenated proteins with a 5-fold excess of ligand in the absence and presence of inositol hexaphosphate. Association rate constants for the individual alpha and beta subunits in the T-state conformation were assigned by measuring time courses for the reaction of a small, limiting amount of CO with a 20-fold excess of deoxyhemoglobin (i.e. Hb4 + CO----Hb4(CO)). The effects of the E7 and E11 mutations in T-state alpha subunits were qualitatively similar to those observed for the same subunit in the R-state (Mathews, A.J., Rohlfs, R.J., Olson, J.S., Tame, J., Renaud, J-P., and Nagai, K. (1989) J. Biol. Chem. 264, 16573-16583). The alpha His58(E7) to Gly and Val62(E11) to Ala substitutions caused 80- and 3-fold increases, respectively, in k'CO for T-state alpha subunits, and the alpha Val62(E11) to Ile mutation caused a 3-fold decrease. The beta His63(E7) to Gly and Val67(E11) to Ala substitutions produced 70- and 8-fold increases, respectively, in k'CO for T-state beta subunits whereas these same mutations caused little effect on the rate of CO binding to R-state beta subunits. The beta Val67(E11) to Ile mutation produced the same large effect, a 23-fold reduction in k'CO, in both quaternary conformations of beta subunits. These kinetic results can be interpreted qualitatively in terms of differences between the alpha and beta subunits in the deoxy and liganded crystal structures of human hemoglobin (Perutz, M.F. (1990) Annu. Rev. Physiol. 52, 1-25). Both the structural and functional data suggest that the distal portion of the beta heme pocket is tightly packed in deoxyhemoglobin whereas the CO binding site in R-state beta subunits is much more open. In contrast, the distal portion of the alpha heme pocket is restricted sterically in both quaternary states.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
2.
P. D. Blanc N. Maizlish P. Hiatt K. R. Olson D. Rempel 《The Western journal of medicine》1990,152(2):181-184
In a study of occupational illness reported to a regional poison control center and to gauge the center''s outreach and services, we did follow-up interviews of 301 case contacts over a 6-month period. We ascertained referral routes, reasons for contacting the poison control center, and awareness of the center''s function. For 122 cases a nonphysician was the initial poison control center contact. Of the nonphysician contacts, 41 had already consulted a health care provider and been referred to the poison control center for assistance. Of the 70 persons with exposure, only 21 had been aware before their exposures that poison control center services might include occupational chemical illness consultation. Physicians and nonphysicians expressed similar reasons for contacting the poison control center, with 118 of 301 identifying the need for an exposure hazard risk assessment. These data suggest that although those contacting a poison control center because of occupational illness include a variety of cases, they have many similar service needs. 相似文献
3.
M E Steinhelper R A Fisher G E Revtyak D J Hanahan M S Olson 《The Journal of biological chemistry》1989,264(19):10976-10981
Vasoconstriction and subsequent glycogenolysis stimulated by immune complex infusion into perfused rat livers was inhibited by prior infusion of isoproterenol. Similarly, isoproterenol inhibited the biosynthesis of bioactive lipid autacoids such as platelet-activating factor, prostaglandin E2, and thromboxane B2 which was stimulated by immune aggregates. The adrenergic receptor specificity of these effects was determined through the use of specific adrenergic subtype-specific agonists and antagonists to be mediated by beta 2-adrenergic receptors. Indirect evidence for the differential expression of hepatic sinusoidal and parenchymal beta-adrenergic receptors in the male rat during ontogeny suggested that inhibition of immune aggregate-stimulated autacoid biosynthesis, vasoconstriction, and glycogenolysis by isoproterenol occurs at a sinusoidal locus, most likely Kupffer cells. In contrast with the ability of beta 2-adrenergic agonists to inhibit immune aggregate- and platelet-activating factor-stimulated hepatic metabolism, dibutyryl cyclic AMP did not mimic these sinusoidal beta 2-adrenergic effects, despite stimulating hepatic parenchymal cell glycogenolysis as effectively as isoproterenol. These observations suggest a role for cyclic AMP-independent mechanisms in the regulation of heterologous stimulus-response coupling by hepatic sinusoidal beta 2-adrenergic receptors. 相似文献
4.
The Rho‐associated (ROCK) serine/threonine kinases have emerged as central regulators of the actomyosin cytoskeleton, their main purpose being to promote contractile force generation. Aided by the discovery of effective inhibitors such as Y27632, their roles in cancer have been extensively explored with particular attention focused on motility, invasion and metastasis. Recent studies have revealed a surprisingly diverse range of functions of ROCK. These insights could change the way ROCK inhibitors might be used in cancer therapy to include the targeting of stromal rather than tumour cells, the concomitant blocking of ROCK and proteasome activity in K‐Ras‐driven lung cancers and the combination of ROCK with tyrosine kinase inhibitors for treating haematological malignancies such as chronic myeloid leukaemia. Despite initial optimism for therapeutic efficacy of ROCK inhibition for cancer treatment, no compounds have progressed into standard therapy so far. However, by carefully defining the key cancer types and expanding the appreciation of ROCK's role in cancer beyond being a cell‐autonomous promoter of tumour cell invasion and metastasis, the early promise of ROCK inhibitors for cancer therapy might still be realized. 相似文献
5.
To advance the development of conservation planning for rare species with small geographic ranges, we determined habitat associations
of Siskiyou Mountains salamanders (Plethodon stormi) and developed habitat suitability models at fine (10 ha), medium (40 ha), and broad (202 ha) spatial scales using available
Geographic Information Systems data and logistic regression analysis with an information theoretic approach. Across spatial
scales, there was very little support for models with structural habitat features, such as tree canopy cover and conifer diameter.
Model-averaged 95% confidence intervals for regression coefficients and associated odds ratios indicated that the occurrence
of Siskiyou Mountains salamanders was positively associated with rocky soils and Pacific madrone (Abutus menziesii) and negatively associated with elevation and white fir (Abies concolor); these associations were consistent across 3 spatial scales. The occurrence of this species also was positively associated
with hardwood density at the medium spatial scale. Odds ratios projected that a 10% decrease in white fir abundance would
increase the odds of salamander occurrence 3.02–4.47 times, depending on spatial scale. We selected the model with rocky soils,
white fir, and Oregon white oak (Quercus garryana) as the best model across 3 spatial scales and created habitat suitability maps for Siskiyou Mountains salamanders by projecting
habitat suitability scores across the landscape. Our habitat suitability models and maps are applicable to selection of priority
conservation areas for Siskiyou Mountains salamanders, and our approach can be easily adapted to conservation of other rare
species in any geographical location. 相似文献
6.
7.
Plant-herbivore chemical signals and behavioral plasticity may enhance parasitoid host-foraging efficacy in the field; however, no studies have quantified the potential benefits from these factors under field-type conditions. The effect of plant-herbivore signals and learning on the foraging efficacy of Microplitis croceipes was quantified by directly observing and recording total and sequential duration of various foraging behaviors relative to 5 randomly placed herbivore-damaged and host-infested cotton plants and 20 undamaged and non-host-infested plants. Microplitis croceipes spent significantly more time searching (flying and antennation) on host infested versus uninfested plants. Antennation time was significantly and negatively correlated with successive host stings. Contrary to expectations of increased duration, flight time remained constant throughout the foraging bout, which may indicate that there was some learning associated with flight. These results suggest that plant-herbivore chemical signals and learning enhances the foraging efficacy of M. croceipes. 相似文献
8.
Obesity-inducing lesions of the central nervous system alter leptin uptake by the blood-brain barrier. 总被引:1,自引:0,他引:1
Leptin regulates body adiposity by decreasing feeding and increasing thermogenesis. Obese humans and some obese rodents are resistant to peripherally administered leptin, suggesting a defect in the transport of leptin across the blood-brain barrier (BBB). Defective transport of exogenous leptin occurs in some models of obesity, but in other models transport is normal. This shows that factors other than obesity are associated with impairment of leptin transport across the BBB. In order to further investigate these factors, we determined leptin transport in rats made obese by lesioning of the ventromedial hypothalamus (VMH), paraventricular nucleus (PVN), or posterodorsal amygdala (PDA). These regions all contain leptin receptors and lesions there induce obesity and hyperleptinemia and alter the levels of many feeding hormones which might participate in leptin transporter regulation. We measured the uptake of radioactively labeled leptin by the BBB by multiple-time regression analysis which divides uptake into a reversible phase (Vi, e.g., receptor/transporter binding to the brain endothelial cell) and an irreversible phase (Ki, complete transport across the BBB). Leptin uptake was not affected in rats with VMH lesions. No significant change occurred in the entry rate (Ki) for any group, although Ki declined by over 35% in rats with PVN lesions. Decreased uptake was observed in rats with PVN lesions and with PDA lesions. This was primarily due to a reduced Vi (about 21% for the PDA). This decreased uptake is most likely explained by decreased binding of leptin to the brain endothelial cell, which could be because of decreased binding by either receptors or transporters. This suggests that some of the feeding hormones controlled by the PVN and PDA may participate in regulating leptin uptake by the BBB. 相似文献
9.
Radioactive 5-desmethylubiquinone-9 has been isolated from mitochondria synthesizing ubiquinone-9-14C from p-hydroxybenzoate-U-14C. By mass spectrometry, the natural 5-desmethylubiquinone-9 has been shown to be identical with that chemically synthesized from fumigatol and solanesol. Synthetic 5-desmethylubiquinone-9-3H can be methylated to ubiquinone-9-3H by S-adenosyl-L-methionine in submitochondrial particles. 相似文献
10.
Messenger RNA orientation on the ribosome. Placement by electron microscopy of antibody-complementary oligodeoxynucleotide complexes 总被引:9,自引:0,他引:9
H M Olson L S Lasater P A Cann D G Glitz 《The Journal of biological chemistry》1988,263(29):15196-15204
Messenger RNA orients on the small ribosomal subunit by base pairing with a complementary sequence in ribosomal RNA. We have positioned this ribosomal RNA segment and thus oriented the mRNA using a new technique--localization of an antibody-recognizable modified complementary oligodeoxynucleotide by electron microscopy. A synthetic oligodeoxynucleotide complementary to the message-positioning ribosomal RNA sequence was modified at either or both ends with different antigenic markers. Electron microscopy of subunit-oligodeoxynucleotide-antibody complexes allowed separate placement of each terminal marker of the oligodeoxynucleotide probe. The 5'-end of the complementary sequence contacts the subunit at the platform tip (rRNA nucleotide 1542). The message then extends along the interior side of the platform to the level of the fork of the cleft separating the platform from the subunit body, and displaced slightly to the convex side of the platform (rRNA nucleotide 1531). Based on our results and data from other laboratories, we propose a model for the positioning of messenger RNA on the 30 S subunit. 相似文献