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131.
Papakonstantinou E; Karakiulakis G; Eickelberg O; Perruchoud AP; Block LH; Roth M 《Glycobiology》1998,8(8):821-830
The formation of atherosclerotic lesions is characterized by invasion of
vascular smooth muscle cells (VSMC) into the tunica intima of the arterial
wall and subsequently by increased proliferation of VSMC, a process
apparently restricted to the intimal layer of blood vessels. Both events
are preceded by the pathological overexpression of several growth factors,
such as platelet-derived growth factor (PDGF) which is a potent mitogen for
VSMC and can induce their chemotaxis. PDGF is generally not expressed in
the normal artery but it is upregulated in atherosclerotic lesions. We have
previously shown that PDGF-BB specifically stimulates proliferating VSMC to
secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence
regarding the biological functions of this glycan. We observed that HA-340
inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent
manner and enhanced the PDGF-dependent invasion of VSMC through a basement
membrane barrier. These effects were abolished following treatment of
HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent
invasion of VSMC coincided with increased secretion of the 72-kDa type IV
collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid
inhibitor of matrix metalloproteinases. HA-340 did not exert any
chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF
gradient. In human atheromatic aortas, we found that HA- 340 is expressed
with a negative concentration gradient from the tunica media to the tunica
intima and the atheromatic plaque. Our findings suggest that HA-340 may be
linked to the pathogenesis of atherosclerosis, by modulating VSMC
proliferation and invasion.
相似文献
132.
Protein evolution in different cellular environments: cytochrome b in sharks and mammals 总被引:4,自引:0,他引:4
DNA sequences for the mitochondrial cytochrome b gene were determined for
13 species of sharks. Rates and patterns of amino acid replacement are
compared for sharks and mammals. Absolute rates of cytochrome b evolution
are six times slower in sharks than in mammals. Bivariate plots of the
number of nonsynonymous and silent transversions are indistinguishable in
the two groups, however, suggesting that the differences in amino acid
replacement rates are due primarily to differences in DNA substitution
rates. Patterns of amino acid replacement are also similar in the two
groups. Conserved and variable regions occur in the same parts of the
cytochrome b gene, and there is little evidence that the types of amino
acid changes are significantly different between the groups. Similarity in
the relative rates and patterns of protein change between the two groups
prevails despite dramatic differences in the cellular environments of
sharks and mammals. Poor penetrance of physiological differences through to
rates of protein evolution provides support for the neutral theory and
suggests that, for cytochrome b, patterns of evolution have been relatively
constant throughout much of vertebrate history.
相似文献
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R. Mouton S. Genade B. Huisamen M. Malan A. Lochner 《Molecular and cellular biochemistry》1992,115(2):195-202
In this study incorporation of [3H]inositol into inositol phosphates and phosphoinositides as well as tissue Ins(1,4,5)P3 levels of the atria and ventricles of isolated, perfused rat hearts were compared. Although the incorporation of [3H]inositol into the phosphoinositides of atria and ventricles was similar, significantly higher (2–3 fold) incorporation rates into inositol phosphates were observed in atrial tissue. Using a D-myo-[3H]Ins(1,4,5)P3 assay system, the Ins(1,4,5)P3 levels observed in atria from perfused rat hearts were also significantly higher than those obtained under the same experimental circumstances in the ventricles.Since previous studies on whole hearts showed inhibition of the phosphatidylinositol (PI) pathway during ischaemia with an immediate significant stimulation upon reperfusion [12, 20], the effects of ischaemia and 1 min postischaemic reperfusion were also examined separately in atria and ventricles. The results showed that 20 min of global ischaemia significantly depressed Ins(1,4,5)P3 levels as well as incorporation of [3H]inositol into ventricular InSP2 and InSP3. Reperfusion caused an immediate (within 1 min) increase in Ins(1,4,5)P3 levels and also [3H]inositol incorporation into all three cytosolic inositol phosphates in the ventricles. However, the effect of ischaemia and reperfusion on Ins(1,4,5)P3 levels as well as the incorporation of [3H]inositol into the inositol phosphates were less prominent in the atria. It therefore appears that the differential responses of the atria and the ventricles to an oxygen deficiency [41] are also reflected in the differences in PI metabolism during ischaemia-reperfusion. 相似文献
137.
Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice 总被引:3,自引:0,他引:3
Nagamine CM; Shiroishi T; Miyashita N; Tsuchiya K; Ikeda H; Takao N; Wu XL; Jin ML; Wang FS; Kryukov AP 《Molecular biology and evolution》1994,11(6):864-874
When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is
replaced by the Y of certain strains of Mus musculus domesticus, testis
determination fails and all XY fetuses develop either as hermaphrodites or
XY females (XY sex reversal). This suggests the presence of at least two
alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6.
The B6 Y chromosome is derived from the Japanese house mouse, M. m.
molossinus and therefore carries a molossinus Sry allele. As a first step
to determine how the molossinus Sry allele evolved, its distribution
pattern was determined in wild mice. The cumulative data of 96 M. musculus
samples obtained from 58 geographical locations in Europe, North Africa,
and Asia show the molossinus Sry allele is restricted to Japan and the
neighboring Asian mainland and confirm that Japanese M. m. molossinus mice
were derived in part from a race of M. m. musculus from Korea or Manchuria.
Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve
as molecular markers for studies on the evolution of wild M. musculus
populations and can help determine the role sex determination plays in
speciation.
相似文献
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Bo Yuan Tamar Harel Shen Gu Pengfei Liu Lydie Burglen Sandra Chantot-Bastaraud Violet Gelowani Christine?R. Beck Claudia?M.B. Carvalho Sau?Wai Cheung Andrew Coe Valérie Malan Arnold Munnich Pilar?L. Magoulas Lorraine Potocki James?R. Lupski 《American journal of human genetics》2015,96(5):691-692
The genomic duplication associated with Potocki-Lupski syndrome (PTLS) maps in close proximity to the duplication associated with Charcot-Marie-Tooth disease type 1A (CMT1A). PTLS is characterized by hypotonia, failure to thrive, reduced body weight, intellectual disability, and autistic features. CMT1A is a common autosomal dominant distal symmetric peripheral polyneuropathy. The key dosage-sensitive genes RAI1 and PMP22 are respectively associated with PTLS and CMT1A. Recurrent duplications accounting for the majority of subjects with these conditions are mediated by nonallelic homologous recombination between distinct low-copy repeat (LCR) substrates. The LCRs flanking a contiguous genomic interval encompassing both RAI1 and PMP22 do not share extensive homology; thus, duplications encompassing both loci are rare and potentially generated by a different mutational mechanism. We characterized genomic rearrangements that simultaneously duplicate PMP22 and RAI1, including nine potential complex genomic rearrangements, in 23 subjects by high-resolution array comparative genomic hybridization and breakpoint junction sequencing. Insertions and microhomologies were found at the breakpoint junctions, suggesting potential replicative mechanisms for rearrangement formation. At the breakpoint junctions of these nonrecurrent rearrangements, enrichment of repetitive DNA sequences was observed, indicating that they might predispose to genomic instability and rearrangement. Clinical evaluation revealed blended PTLS and CMT1A phenotypes with a potential earlier onset of neuropathy. Moreover, additional clinical findings might be observed due to the extra duplicated material included in the rearrangements. Our genomic analysis suggests replicative mechanisms as a predominant mechanism underlying PMP22-RAI1 contiguous gene duplications and provides further evidence supporting the role of complex genomic architecture in genomic instability. 相似文献