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21.
Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase 总被引:3,自引:0,他引:3
C Ged D R Umbenhauer T M Bellew R W Bork P K Srivastava N Shinriki R S Lloyd F P Guengerich 《Biochemistry》1988,27(18):6929-6940
A cytochrome P-450 (P-450) multigene family codes for several related human liver enzymes, including the P-450 responsible for (S)-mephenytoin 4'-hydroxylation. This enzyme activity has previously been shown to be associated with a genetic polymorphism. Genomic (Southern) blot analysis using non-overlapping 5' and 3' portions of a cDNA clone suggests that approximately seven related sequences are present in this gene family. In this study four cDNA clones, all nearly full-length, were isolated from a bacteriophage lambda gt11 library prepared from a single human liver. These clones can be grouped into two categories that are approximately 85% identical at the level of DNA sequence. The cDNA clones in one category (MP-4, MP-8) both match the N-terminal sequences of the P-450MP-1 and P-450MP-2 proteins, which had previously been shown to be catalytically active in (S)-mephenytoin 4'-hydroxylation. These two cDNAs, MP-4 and MP-8, differ in only two bases in the coding region but are quite distinct in their 3' noncoding regions. Another protein (P-450MP-3) was isolated on the basis of its immunochemical similarity to P-450MP-1 but was found to be catalytically inactive; amino acid sequencing of tryptic peptides of P-450MP-3 showed a correspondence to the second category of cDNA clones (MP-12, MP-20), which differ from each other in only four (nonsilent) base changes. Oligonucleotides specific for the two groups of cDNA clones were used as probes of human liver mRNAs--individual liver samples examined expressed both types of mRNAs but no correlation was observed between the abundance levels of any mRNA and catalytic activity. Further, oligonucleotide probes indicated that mRNAs corresponding to both the MP-4 and MP-8 clones were apparently present in individual liver samples. A monoclonal antibody was isolated that recognized P-450MP-1 but not P-450MP-2 or P-450MP-3; the amount of protein detected by the antibody in different liver samples was not correlated with the mephenytoin 4'-hydroxylase activity. These results indicate that several closely related P-450 genes are all expressed in individual human livers. The MP-4/MP-8 gene products are proposed to be the ones most likely involved in mephenytoin 4'-hydroxylation, and much of the variation in catalytic activity among individuals is not a result of differences in levels of P-450MP-1 or mRNA but may be due to base differences in the structural gene(s). 相似文献
22.
Liquid membrane bilayers, generated by bacteriorhodopsin on a supporting membrane, exhibit photo osmosis. The phenomenon has been shown to be a consequence of light-induced electrical potential differences which develop across the liquid membrane bilayer due to the light-driven proton pumping action of bacteriorhodopsin. The variations of photo osmotic velocity with wavelength, intensity of light, and proton acceptor concentrations has been studied. 相似文献
23.
The reaction of a photoaffinity analog, 3'-O-(4-benzoyl)-benzoic-adenosine 5'-triphosphate (BZ2ATP) with gizzard myosin is described. The incorporation of BZ2ATP into myosin is both specific and stoichiometric. About 2.2 mol BZ2ATP are incorporated/mol myosin resulting in the significant loss of EDTA(K+) ATPase activity. The Mg2+ and actin-activated ATPase activities are slightly inhibited. Addition of ATP (millimolar) during the photolysis reaction significantly inhibits incorporation of BZ2ATP into myosin. Our data show that the label is mainly incorporated into the heavy chain of myosin with some label in the 20-kDa light chain. Limited proteolysis of radioactively labeled myosin subfragment 1 with trypsin reveals the presence of radioactivity mainly in the 50-kDa fragment and some in the 29-kDa and 25-kDa fragments. However, our data on the ATP-sensitive incorporation of BZ2ATP into the tryptic fragments suggest that the 50-kDa peptide, not the 29-kDa peptide, may be located at or around the active site. 相似文献
24.
P N Srivastava K Arbtan G H Takei T T Huang R Yanagimachi 《Biochemical and biophysical research communications》1986,137(3):1061-1068
Alpha-L-fucosidase was purified from the bull seminal plasma by chromatography on DEAE-disk, octyl sepharose hydrophobic column and HPLC. The enzyme appeared to be pure as judged by the polyacrylamide gel electrophoresis both under the nondenaturing and denaturing conditions. The pure enzyme promoted the acrosome reaction of guinea pig spermatozoa in vitro. This is the first report showing that an acrosomal enzyme induces acrosome reaction which is an essential pre-requisite for the gamete interaction and fertilization. 相似文献
25.
G T Bowman J J Clement D E Davidson V Eswarakrishnan L Field J M Hoch H A Musallam R O Pick R Ravichandran P K Srivastava 《Chemico-biological interactions》1986,57(2):161-174
Capabilities are reported of di- and higher sulfides (RSnR') terminated by sulfinate functions [-S(O)O-] for protecting mice against otherwise lethal effects of ionizing radiation. With the use of congeners, structure-activity correlations are developed for the effects of esterification of the sulfinate function, of changing the length of the chain of sulfur atoms, of reduction to a mercapto sulfinate, and of changing the substituents R and R' to chiral and other types of groups. Neither a trisulfide nor a sulfinate by itself was significantly radioprotective. The key requirement for radio-protection in the series appears to be the presence of a sulfur function (-Sn-) from which a thiol can be engendered by a neighboring-group effect of an electron-donating group; sulfoxide functions may afford alternatives to sulfinate functions as such neighboring groups. The relevance of structure-activity relations to the chemical and biological mechanisms involved in the radioprotective activities is discussed. 相似文献
26.
Syed M. I. Kazmi Jai Ramwani Lalit K. Srivastava G. Rajakumar Gregory M. Ross Marjorie Cullen Ram K. Mishra 《Journal of neurochemistry》1986,47(5):1493-1502
3,4-Dihydroxyphenylethylamine (dopamine) D2 receptors, solubilized from bovine striatal membranes using a cholic acid-NaCl combination, exhibited the typical pharmacological characteristics of both agonist and antagonist binding. The rank order potency of the agonists and antagonists to displace [3H]spiroperidol binding was the same as that observed with membrane-bound receptors. Computer-assisted analysis of the [3H]spiroperidol/agonist competition curves revealed the retention of high- and low-affinity states of the D2 receptor in the solubilized preparations and the proportions of receptor subpopulations in the two affinity states were similar to those reported in membrane. Guanine nucleotide almost completely converted the high-affinity sites to low-affinity sites for the agonists. The binding of the high-affinity agonist [3H]N-n-propylnorapomorphine ([3H]NPA) was clearly demonstrated in the solubilized preparations for the first time. Addition of guanylyl-imidodiphosphate completely abolished the [3H]NPA binding. When the solubilized receptors were subjected to diethylaminoethyl-Sephacel chromatography, the dopaminergic binding sites eluted in two distinct peaks, showing six- to sevenfold purification of the receptors in the major peak. Binding studies performed on both peaks indicated that the receptor subpopulation present in the first peak may have a larger proportion of high-affinity binding sites than the second peak. The solubilized preparation also showed high-affinity binding of [35S]guanosine-5'-(gamma-thio)triphosphate, a result suggesting the presence of guanine nucleotide binding sites, which may interact with the solubilized D2 receptors. These data are consistent with the retention of the D2 receptor-guanine nucleotide regulatory protein complex in the solubilized preparations and should provide a suitable model system to study the receptor-effector interactions. 相似文献
27.
Flow of couple stress fluid through stenotic blood vessels 总被引:3,自引:0,他引:3
L M Srivastava 《Journal of biomechanics》1985,18(7):479-485
The effects of an axially symmetric mild stenosis on the flow of blood, when blood is represented by a couple stress fluid model, have been studied. It is found that, for a fixed stenosis size, the resistance to flow and wall shear stress increase as the couple stress parameter eta decreases from unity. A comparison of the results with those of the Newtonian case shows that the magnitude of resistance to flow and wall shear under a given set of conditions, is greater in the case of the couple stress fluid model. It is seen that even in the case of a mild stenosis (19% area reduction), resistance to flow and wall shear values are increased over those for no stenosis by 60% and 62%, respectively, when compared with the case of a Newtonian fluid. 相似文献
28.
Regulation of toxin biosynthesis by plasmids in Vibrio cholerae 总被引:2,自引:0,他引:2
A A Khan R Srivastava V B Sinha B S Srivastava 《Journal of general microbiology》1985,131(10):2653-2657
Vibrio cholerae strain 569B Inaba harbouring P plasmid produced less toxin than the parent strain. To examine the effect of plasmid loss on toxin production, temperature-sensitive (ts) mutants of P, unable to replicate at 42 degrees C, were isolated. One ts plasmid was unstable at 42 degrees C and its loss yielded a cured strain that resumed a normal level of toxin biosynthesis characteristic of the plasmid-free parent strain. Toxin production was again suppressed in the cured strain after reacquisition of P plasmid. This suggested a role for plasmid-borne genes in the regulation of toxin biosynthesis. A mutant of strain 569B Inaba that produced mutant toxin was isolated by transfer of P and V plasmids. The mutant toxin was similar to choleragenoid because it did not give rise to symptoms of cholera but induced antitoxin immunity in rabbits. 相似文献
29.
c-Ha-ras-1 proto-oncogene amplification and overexpression during the limited replicative life span of normal human fibroblasts 总被引:6,自引:0,他引:6
A Srivastava J S Norris R J Shmookler Reis S Goldstein 《The Journal of biological chemistry》1985,260(10):6404-6409
The cellular proto-oncogene c-Ha-ras-1 undergoes up to 4-fold amplification during the limited replicative life span of normal human diploid fibroblasts in vitro. Levels of c-Ha-ras-1 messenger RNA and its p21 protein product are correspondingly elevated. Cellular proto-oncogene amplification and overexpression, although frequently associated with tumorigenesis, may thus occur during normal cellular growth. 相似文献
30.
Short-term metabolic and concomitant morphologic effects of streptozotocin diabetes on isoproterenol-induced myocardial infarction
was studied in Wistar rats, Of particular significance was the observation that myocardial infarction in concert with diabetes
brought about a distinctive exacerbation of the severity and complexity of the histopathological lesions. Of all the biochemical
parameters, serum glucose and free fatty acids registered maximum elevation and serum lactate and cardiac glycogen levels
a maximum reduction. Among the lipoproteins, an inverse relationship was found between high density lipoproteins and low density
and very low density lipoproteins; while high density lipoproteins, ratio of high density lipoprotein to low density lipoprotein
and the percentage of high density lipoprotein were decreased, there was a significant increase in low density lipoprotein
concentration and percentage values of low density and very low density lipoproteins. In diabetes, the B cell of the endocrine
pancreas depicted selective necrosis. Loss of insulin granules and wide-spread necrobiosis of cellular elements of the pancreatic
islets were observed, respectively, in myocardial infarction and in diabetes plus myocardial infarction combinations. Pathological
evidence of chemical-induced mild toxicity was present in the exocrine parenchyma. Mitotic features and the presence of centroacinar
cells in the damaged Langerhans’ islets supposedly formed the basis of regeneration of the tissue in diabetes, with or without
vascular complications 相似文献