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21.
M. Adrin Troncoso-Ponce Nicholas J. Kruger George Ratcliffe Rafael Garcs Enrique Martínez-Force 《Phytochemistry》2009,70(9):1117-1122
Unlike other oilseeds (e.g. Arabidopsis), developing sunflower seeds do not accumulate a lot of starch and they rely on the sucrose that comes from the mother plant to synthesise lipid precursors. Between 10 and 25 days after flowering (DAF), when sunflower seeds form and complete the main period of storage lipid synthesis, the sucrose content of seeds is relatively constant. By contrast, the glucose and fructose content falls from day 20 after flowering and it is always lower than that of sucrose, with glucose being the minor sugar at the end of the seed formation. By studying the apparent kinetic parameters and the activity of glycolytic enzymes in vitro, it is evident that all the components of the glycolytic pathway are present in the crude seed extract. However, in isolated plastids important enzymatic activities are missing, such as the glyceraldehyde-3-phosphate dehydrogenase, involved in the conversion of glyceraldehyde 3-phosphate into 1,3-biphospho-glycerate, or the enolase that converts 2-phosphoglycerate into phosphoenolpyruvate. Hence, phosphoenolpyruvate or one of its derivatives, like pyruvate and malate from the cytosol, may be the primary carbon sources for lipid biosynthesis. Accordingly, the glucose-6-P imported into the plastid is likely to be used in the pentose phosphate pathway to produce the reducing power for lipid biosynthesis in the form of NADPH. Data from crude seed extracts indicate that enolase activity increased during seed formation, from 16 days after flowering, and that this activity was well correlated with the period of storage lipid synthesis. In addition, while the presence of some glycolytic enzymes increased during lipid synthesis, others decreased, remained constant, or displayed irregular temporal behaviour. 相似文献
22.
Kenneth A. Marx Ray Kruger Michael J. Clarke 《Molecular and cellular biochemistry》1989,86(2):155-162
The goal of this study is to establish the nature of pentammineruthenium(III) binding to DNA in intact mouse liver nuclei. Also, we wish to determine whether the nucleosomal organization of mouse chromatin has a substantial effect on the relative Ru(III) binding levels of internucleosomal and nucleosomal core DNA. These questions are important because ammineruthenium compounds share chemical and biological properties with the cis-dichlorodiammineplatinum(II) or cisplatin chemotherapeutic agent. Therefore, they represent a potential class of new chemotherapeutic agents. We find that in intact nuclei the predominant DNA binding site for pentammineruthenium(II), followed by air oxidation to pentammineruthenium(III), is N-7 guanine, as is the case with cisplatin. Also, the Ru(III) distribution between internucleosomal and nucleosomal core DNA was found to be nearly identical as probed with three non-specific deoxyribonucleases. 相似文献
23.
L. J. Sweetlove R. Dunford R. G. Ratcliffe N. J. Kruger 《Plant, cell & environment》2000,23(8):873-881
The aim of this work was to investigate the effect of decreased activity of lactate dehydrogenase (EC 1.1.1.27; LDH) on lactate metabolism in potato tubers. By expressing a cDNA‐encoding potato tuber LDH in the antisense orientation, we generated transgenic potato plants with a preferential decrease in two of the five isozymes of LDH. Surprisingly, transgenic tubers grown under normoxic conditions did not contain less lactate, but rather instead contained approximately two‐fold more lactate than control tubers. This result is explicable if the decreased isozymes of LDH are responsible for the oxidation of lactate to pyruvate in vivo. This was confirmed by measurements of the rate of metabolism of lactate supplied to tuber discs: the rate in transgenic tubers was approximately half that of control tubers. The decrease in LDH activity had no measurable effect on the accumulation of lactate in cold‐stored tubers under anoxia, nor during the subsequent utilization of this lactate upon return to normoxia. In both control and transgenic tubers, the accumulation of lactate during anoxia was not accompanied by an induction of LDH activity or a change in isozyme distribution. In contrast, the metabolism of lactate after a period of anoxia was accompanied by a two‐fold increase in LDH activity and the induction of two isozymes that were distinct from those which had been decreased in the transgenic plants. 相似文献
24.
Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line. 总被引:3,自引:1,他引:3 下载免费PDF全文
R DePinho K Kruger N Andrews S Lutzker D Baltimore F W Alt 《Molecular and cellular biology》1984,4(12):2905-2910
We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from mu to gamma 2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed VHDJH region and the C gamma 2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S mu and S gama 2b regions and resulted in the loss of the C mu gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S mu region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the gamma 2b-producing line retained two copies of the C mu gene and two copies of the sequence just 5' to the S gamma 2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed. 相似文献
25.
Turkseven S Kruger A Mingone CJ Kaminski P Inaba M Rodella LF Ikehara S Wolin MS Abraham NG 《American journal of physiology. Heart and circulatory physiology》2005,289(2):H701-H707
Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion (O2-) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, O2-, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) levels and vascular responses to ACh in control and diabetic rats. Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats (P < 0.05). Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD. Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein. Increased HO-1 activity in diabetic rats was associated with a decrease in iNOS but increases in eNOS and plasma catalase activity. On the other hand, aortic ring segments from diabetic rats exhibited a significant reduction in vascular relaxation to ACh, which was reversed with cobalt protoporphyrin treatment. These data demonstrate that an increase in HO-1 protein and activity, i.e., CO and bilirubin production, in diabetic rats brings about a robust increase in EC-SOD, catalase, and eNOS with a concomitant increase in endothelial relaxation and a decrease in O2-. These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase. 相似文献
26.
27.
Glenn S. Van Aller Nicolas Reynoird Olena Barbash Michael Huddleston Shichong Liu Anne-Flore Zmoos Patrick McDevitt Robert Sinnamon BaoChau Le Gloria Mas Roland Annan Julien Sage Benjamin A. Garcia Peter J. Tummino Or Gozani Ryan G. Kruger 《Epigenetics》2012,7(4):340-343
Smyd3 is a lysine methyltransferase implicated in chromatin and cancer regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5 (H4K5me). This novel histone methylation mark is detected in diverse cell types and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3-driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via H4K5 methylation, provides a potential new link between chromatin dynamics and neoplastic disease. 相似文献
28.
Large, rapidly evolving intergenic spacers in the mitochondrial DNA of the salamander family Ambystomatidae (Amphibia: Caudata) 总被引:3,自引:2,他引:3
We report the presence, in the mitochondrial DNA (mtDNA) of all of the
sexual species of the salamander family Ambystomatidae, of a shared 240- bp
intergenic spacer between tRNAThr and tRNAPro. We place the intergenic
spacer in context by presenting the sequence of 1,746 bp of mtDNA from
Ambystoma tigrinum tigrinum, describe the nucleotide composition of the
intergenic spacer in all of the species of Ambystomatidae, and compare it
to other coding and noncoding regions of Ambystoma and several other
vertebrate mtDNAs. The nucleotide substitution rate of the intergenic
spacer is approximately three times faster than the substitution rate of
the control region, as shown by comparisons among six Ambystoma
macrodactylum sequences and eight members of the Ambystoma tigrinum
complex. We also found additional inserts within the intergenic spacers of
five species that varied from 87-444 bp in length. The presence of the
intergenic spacer in all sexual species of Ambystomatidae suggests that it
arose at least 20 MYA and has been a stable component of the ambystomatid
mtDNA ever since. As such, it represents one of the few examples of a large
and persistent intergenic spacer in the mtDNA of any vertebrate clade.
相似文献
29.
Laishram R. Singh Sapna Gupta Nicholaas H. Honig Jan P. Kraus Warren D. Kruger 《PLoS genetics》2010,6(1)
Missense mutant proteins, such as those produced in individuals with genetic diseases, are often misfolded and subject to processing by intracellular quality control systems. Previously, we have shown using a yeast system that enzymatic function could be restored to I278T cystathionine β-synthase (CBS), a cause of homocystinuria, by treatments that affect the intracellular chaperone environment. Here, we extend these studies and show that it is possible to restore significant levels of enzyme activity to 17 of 18 (94%) disease causing missense mutations in human cystathionine β-synthase (CBS) expressed in Saccharomyces cerevisiae by exposure to ethanol, proteasome inhibitors, or deletion of the Hsp26 small heat shock protein. All three of these treatments induce Hsp70, which is necessary but not sufficient for rescue. In addition to CBS, these same treatments can rescue disease-causing mutations in human p53 and the methylene tetrahydrofolate reductase gene. These findings do not appear restricted to S. cerevisiae, as proteasome inhibitors can restore significant CBS enzymatic activity to CBS alleles expressed in fibroblasts derived from homocystinuric patients and in a mouse model for homocystinuria that expresses human I278T CBS. These findings suggest that proteasome inhibitors and other Hsp70 inducing agents may be useful in the treatment of a variety of genetic diseases caused by missense mutations. 相似文献
30.
Many human diseases are caused by missense substitutions that result in
misfolded proteins that lack biological function. Here we express a mutant
form of the human cystathionine β-synthase protein, I278T, in
Saccharomyces cerevisiae and show that it is possible to dramatically
restore protein stability and enzymatic function by manipulation of the
cellular chaperone environment. We demonstrate that Hsp70 and Hsp26 bind
specifically to I278T but that these chaperones have opposite biological
effects. Ethanol treatment induces Hsp70 and causes increased activity and
steady-state levels of I278T. Deletion of the SSA2 gene, which
encodes a cytoplasmic isoform of Hsp70, eliminates the ability of ethanol to
restore function, indicating that Hsp70 plays a positive role in proper I278T
folding. In contrast, deletion of HSP26 results in increased I278T
protein and activity, whereas overexpression of Hsp26 results in reduced I278T
protein. The Hsp26-I278T complex is degraded via a
ubiquitin/proteosome-dependent mechanism. Based on these results we propose a
novel model in which the ratio of Hsp70 and Hsp26 determines whether misfolded
proteins will either be refolded or degraded.Cells have evolved quality control systems for misfolded proteins,
consisting of molecular chaperones (heat shock proteins) and proteases. These
molecules help prevent misfolding and aggregation by either promoting
refolding or by degrading misfolded protein molecules
(1). In eukaryotic cells, the
Hsp70 system plays a critical role in mediating protein folding. Hsp70 protein
interacts with misfolded polypeptides along with co-chaperones and promotes
refolding by repeated cycles of binding and release requiring the hydrolysis
of ATP (2). Small heat shock
proteins (sHsp)2 are
small molecular weight chaperones that bind non-native proteins in an
oligomeric complex and whose function is poorly understood
(3). In mammalian cells, the
sHsp family includes the α-crystallins, whose orthologue in
Saccharomyces cerevisiae is Hsp26. Studies suggest that Hsp26 binding
to misfolded protein aggregates is a prerequisite for effective disaggregation
and refolding by Hsp70 and Hsp104
(4,
5).Misfolded proteins can result from missense substitutions such as those
found in a variety of recessive genetic diseases, including cystathionine
β-synthase (CBS) deficiency. CBS is a key enzyme in the
trans-sulfuration pathway that converts homocysteine to cysteine
(6). Individuals with CBS
deficiency have extremely elevated levels of plasma total homocysteine,
resulting in a variety of symptoms, including dislocated lenses, osteoporosis,
mental retardation, and a greatly increased risk of thrombosis
(7). Approximately 80% of the
mutations found in CBS-deficient patients are point mutations that are
predicted to cause missense substitutions in the CBS protein
(8). The most common mutation
found in CBS-deficient patients, an isoleucine to threonine substitution at
amino acid position 278 (I278T), has been observed in nearly one-quarter of
all CBS-deficient patients. Based on the crystal structure of the catalytic
core of CBS, this mutation is located in a β-sheet more than 10 Å
distant from the catalytic pyridoxal phosphate and does not directly affect
the catalytic binding pocket or the dimer interface
(9).Previously, our lab has developed a yeast bioassay for human CBS
in which yeast expressing functional human CBS can grow in media lacking
cysteine, whereas yeast expressing mutant CBS cannot
(10). We have used this assay
to characterize the functional effects of many different CBS missense alleles,
including I278T (7,
11). However, an unexpected
finding was that it was possible to restore function to I278T and a number of
other CBS missense mutations by either truncation or the addition of a second
missense mutation in the C-terminal regulatory domain
(12,
13). The ability to restore
function by a cis-acting second mutation suggested to us that it
might be possible to restore function in trans via either interaction
of mutant CBS with a small molecule (i.e. drug) or a mutation in
another yeast gene. In a previous study, we found that small osmolyte chemical
chaperones could restore function to mutant CBS presumably by directly
stabilizing the mutant CBS protein
(14).In this study we report on the surprising finding that exposure of yeast to
ethanol can restore function of I278T CBS by altering the ratio of the
molecular chaperones Hsp26 and Hsp70. We demonstrate Hsp70 binding promotes
I278T folding and activity, whereas Hsp26 binding promotes I278T degradation
via the proteosome. By manipulating the levels of Hsp26 and Hsp70, we are able
to show that I278T CBS protein can have enzymatic activity restored to near
wild-type levels of activity. Our findings suggest a novel function for
sHsps. 相似文献