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1.
L V Melendez M D Daniel H H Barahona C E Fraser R D Hunt F G Garcia 《Laboratory animal science》1971,21(6):1050-1054
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Direct sequencing of the mitochondrial displacement loop (D-loop) of shrews
(genus Sorex) for the region between the tRNA(Pro) and the conserved
sequence block-F revealed variable numbers of 79-bp tandem repeats. These
repeats were found in all 19 individuals sequenced, representing three
subspecies and one closely related species of the masked shrew group (Sorex
cinereus cinereus, S. c. miscix, S. c. acadicus, and S. haydeni) and an
outgroup, the pygmy shrew (S. hoyi). Each specimen also possessed an
adjacent 76-bp imperfect copy of the tandem repeats. One individual was
heteroplasmic for length variants consisting of five and seven copies of
the 79-bp tandem repeat. The sequence of the repeats is conducive to the
formation of secondary structure. A termination-associated sequence is
present in each of the repeats and in a unique sequence region 5' to the
tandem array as well. Mean genetic distance between the masked shrew taxa
and the pygmy shrew was calculated separately for the unique sequence
region, one of the tandem repeats, the imperfect repeat, and these three
regions combined. The unique sequence region evolved more rapidly than the
tandem repeats or the imperfect repeat. The small genetic distance between
pairs of tandem repeats within an individual is consistent with a model of
concerted evolution. Repeats are apparently duplicated and lost at a high
rate, which tends to homogenize the tandem array. The rate of D- loop
sequence divergence between the masked and pygmy shrews is estimated to be
15%-20%/Myr, the highest rate observed in D-loops of mammals. Rapid
sequence evolution in shrews may be due either to their high metabolic rate
and short generation time or to the presence of variable numbers of tandem
repeats.
相似文献
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大鼠胼胝体内神经肽Y免疫反应阳性纤维的发育 总被引:1,自引:0,他引:1
本实验用免疫组织化学ABC法研究了大鼠胼胝体内神经肽Y免疫反应阳性(NPY-IR)纤维的生后发育。结果发现,许多NPY-IR纤维在大鼠出生时便存在于胼胝体内。NPY-IR胼胝体纤维的密度在生后1周内继续逐渐增高,在第2周内达到最高峰。之后,NPY-IR胼胝体纤维的密度逐渐下降,至第3周末时接近成年时的水平,即仅有少量NPY-IR纤维存在于胼胝体内。这些结果提示在大鼠早期生后发育过程中许多NPY-IR胼胝体纤维是暂时性的,其作用可能与大脑皮质的机能发育有关。 相似文献
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Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production 总被引:24,自引:0,他引:24
Li N Ragheb K Lawler G Sturgis J Rajwa B Melendez JA Robinson JP 《The Journal of biological chemistry》2003,278(10):8516-8525
Inhibition of mitochondrial respiratory chain complex I by rotenone had been found to induce cell death in a variety of cells. However, the mechanism is still elusive. Because reactive oxygen species (ROS) play an important role in apoptosis and inhibition of mitochondrial respiratory chain complex I by rotenone was thought to be able to elevate mitochondrial ROS production, we investigated the relationship between rotenone-induced apoptosis and mitochondrial reactive oxygen species. Rotenone was able to induce mitochondrial complex I substrate-supported mitochondrial ROS production both in isolated mitochondria from HL-60 cells as well as in cultured cells. Rotenone-induced apoptosis was confirmed by DNA fragmentation, cytochrome c release, and caspase 3 activity. A quantitative correlation between rotenone-induced apoptosis and rotenone-induced mitochondrial ROS production was identified. Rotenone-induced apoptosis was inhibited by treatment with antioxidants (glutathione, N-acetylcysteine, and vitamin C). The role of rotenone-induced mitochondrial ROS in apoptosis was also confirmed by the finding that HT1080 cells overexpressing magnesium superoxide dismutase were more resistant to rotenone-induced apoptosis than control cells. These results suggest that rotenone is able to induce apoptosis via enhancing the amount of mitochondrial reactive oxygen species production. 相似文献
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Incorporation of fluorine into proteins has long served as a means of probing structure and function, yet there are few studies that examine the impact of fluorine substitution, particularly at locations distant from the active sites of enzymes. The flexibility of isomeric fluorine incorporation at Phe is used to explore subtle substitution effects on enzyme activity and conformation. The unnatural amino acids o-, m-, and p-fluorophenylalanines were incorporated biosynthetically into the representative PvuII restriction endonuclease. Interestingly, m-fluoro-Phe-PvuII endonuclease exhibits very similar conformational stability to that of the native enzyme, but it exhibits a reproducible, 2-fold higher average specific activity. Given the level of incorporation and the distribution of species, the species of modified enzyme responsible for this increase in specific activity is most likely even faster. Further, moving the fluorine atom from the meta- to the para-position of Phe results in a 4-fold decrease in specific activity and a decrease in conformational stability of 1.5 kcal/mol. Since none of the Phe residues in PvuII endonuclease lies near the DNA recognition or catalytic sites, this differential behavior alludes to the impact of subtle changes in enzyme conformation on endonuclease activity and suggests novel ways to influence catalytic behavior. 相似文献
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Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion kinase in cardiac remodeling 总被引:8,自引:0,他引:8
Melendez J Welch S Schaefer E Moravec CS Avraham S Avraham H Sussman MA 《The Journal of biological chemistry》2002,277(47):45203-45210
Cellular remodeling during progression of dilation involves focal adhesion contact reorganization. However, the signaling mechanisms and structural consequences leading to impaired cardiomyocyte adhesion are poorly defined. These events were studied in tropomodulin-overexpressing transgenic mice that develop dilated cardiomyopathy associated with chronic elevation of intracellular calcium. Analysis of tropomodulin-overexpressing transgenic hearts by immunoblot and confocal microscopy revealed activation and redistribution of signaling molecules known to regulate adhesion. Calcium-dependent pyk2/related focal adhesion tyrosine kinase (RAFTK) showed changes in expression and phosphorylation state, similar to changes observed for a related downstream target molecule of pyk2/RAFTK termed focal adhesion kinase. Paxillin, the target substrate molecule for focal adhesion kinase phosphorylation, was redistributed in tropomodulin-overexpressing transgenic hearts with enhanced paxillin phosphorylation and cleavage. Certain aspects of the in vivo signaling phenotype including increased paxillin phosphorylation could be recapitulated in vitro using neonatal rat cardiomyocytes infected with recombinant adenovirus to overexpress tropomodulin. In addition, increasing intracellular calcium levels with ionomycin induced pyk2/RAFTK phosphorylation, and adenovirally mediated expression of wild-type pyk2/RAFTK resulted in increased phospho-pyk2/RAFTK levels and concomitant paxillin phosphorylation. Collectively, these results delineate a cardiomyocyte signaling pathway associated with dilation that has potential relevance for cardiac remodeling, focal adhesion reorganization, and loss of contractility. 相似文献