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201.
First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure 下载免费PDF全文
Jaspers NG Raams A Silengo MC Wijgers N Niedernhofer LJ Robinson AR Giglia-Mari G Hoogstraten D Kleijer WJ Hoeijmakers JH Vermeulen W 《American journal of human genetics》2007,80(3):457-466
Nucleotide excision repair (NER) is a genome caretaker mechanism responsible for removing helix-distorting DNA lesions, most notably ultraviolet photodimers. Inherited defects in NER result in profound photosensitivity and the cancer-prone syndrome xeroderma pigmentosum (XP) or two progeroid syndromes: Cockayne and trichothiodystrophy syndromes. The heterodimer ERCC1-XPF is one of two endonucleases required for NER. Mutations in XPF are associated with mild XP and rarely with progeria. Mutations in ERCC1 have not been reported. Here, we describe the first case of human inherited ERCC1 deficiency. Patient cells showed moderate hypersensitivity to ultraviolet rays and mitomycin C, yet the clinical features were very severe and, unexpectedly, were compatible with a diagnosis of cerebro-oculo-facio-skeletal syndrome. This discovery represents a novel complementation group of patients with defective NER. Further, the clinical severity, coupled with a relatively mild repair defect, suggests novel functions for ERCC1. 相似文献
202.
Wittke A Chang A Froicu M Harandi OF Weaver V August A Paulson RF Cantorna MT 《Archives of biochemistry and biophysics》2007,460(2):306-313
Mice lacking the vitamin D receptor (VDR) are resistant to airway inflammation. Pathogenic immune cells capable of transferring experimental airway inflammation to wildtype (WT) mice are present and primed in the VDR KO mice. Furthermore, the VDR KO immune cells homed to the WT lung in sufficient numbers to induce symptoms of asthma. Conversely, WT splenocytes, Th2 cells and hematopoetic cells induced some symptoms of experimental asthma when transferred to VDR KO mice, but the severity was less than that seen in the WT controls. Interestingly, experimentally induced vitamin D deficiency failed to mirror the VDR KO phenotype suggesting there might be a difference between absence of the ligand and VDR deficiency. Lipopolysaccharide (LPS) induced inflammation in the lungs of VDR KO mice was also less than in WT mice. Together the data suggest that vitamin D and the VDR are important regulators of inflammation in the lung and that in the absence of the VDR the lung environment, independent of immune cells, is less responsive to environmental challenges. 相似文献
203.
Magda Tušek Žnidarič Anja Pucer Tanja Fatur Metka Filipič Janez Ščančar Ingrid Falnoga 《Biometals》2007,20(5):781-792
Astroglia cells structurally and nutritionally support neurons in the central nervous system. They play an important role
in guiding the construction of the nervous system and controlling the chemical and ionic environment of neurons. They also
represent the major sites for accumulation and immobilisation of toxic metal ions most probably connected with metallothioneins.
For this reason astroglia cells possess high cytosolic levels of metallothioneins I, II and III (MT-I,II,III). Our aim was
to establish the inducibility and metal binding of MTs in two human astrocytoma cell lines, U87 MG (astrocytoma–glioblastoma,
grade IV) and IPDDC-2A (astrocytoma, grade II), on exposure to cadmium chloride (1 μM). MTs were identified by molecular weight (size exclusion chromatography) and their metal content (Cd, Zn and Cu) to follow
the interactions between metals. We showed that MTs are constitutively expressed in both human astrocytoma cell lines. In
accordance with the higher malignancy grade of U87 MG, the amount of MTs was higher in U87 MG than in IPDDC-2A cells. After
24 hours of exposure to Cd their expression greatly increased in both cell lines and they were capable of immobilising almost
all water soluble Cd. Induction of MTs in U87 MG cells was additionally followed up to 48 hours with exposure to different
concentrations of CdCl2 (1, 10 μM). Induction was a time dependent process throughout the period. Isoform III (identified by chromatographic separation of
isoform III from I/II) was present at all exposure times, but only in traces with respect to the prevailing amounts of MT-I/II
isoforms. So induction can be attributed to isoform I/II only. 相似文献
204.
Saturated free fatty acid (FFA) is a major source of metabolic stress that activates the c-Jun NH(2)-terminal kinase (JNK). This FFA-stimulated JNK pathway is relevant to hallmarks of metabolic syndrome, including insulin resistance. Here we used gene ablation studies in mice to demonstrate a central role for mixed-lineage protein kinases (MLK) in this signaling pathway. Saturated FFA causes protein kinase C (PKC)-dependent activation of MLK3 that subsequently causes increased JNK activity by a mechanism that requires the MAP kinase kinases MKK4 and MKK7. Loss of PKC, MLK3, MKK4, or MKK7 expression prevents FFA-stimulated JNK activation. Together, these data establish a signaling pathway that mediates effects of metabolic stress on insulin resistance. 相似文献
205.
White spot syndrome virus (WSSV) has been a major cause of shrimp mortality in aquaculture worldwide in the past decades. In this study, WSSV infection (by immersion) and behaviour recruitment of haemocytes is investigated in gills and midgut, using an antiserum against the viral protein VP28 and a monoclonal antibody recognising haemocytes (WSH8) in a double immunohistochemical staining and in addition transmission electron microscopy was applied. More WSH 8(+) haemocytes were detected at 48 and 72 h post-infection in the gills of infected shrimp compared to uninfected animals. Haemocytes in the gills and midgut were not associated with VP28-immunoreactivity. In the gills many other cells showed virus replication in their nuclei, while infected nuclei in the gut cells were rare. Nevertheless, the epithelial cells in the midgut showed a clear uptake of VP28 and accumulation in supranuclear vacuoles (SNV) at 8h post-infection. However, epithelial nuclei were never VP28-immunoreactive and electron microscopy study suggests degradation of viral-like particles in the SNV. In contrast to the gills, the midgut connective tissue shows a clear increase in degranulation of haemocytes, resulting in the appearance of WSH8-immunoreactive thread-like material at 48 and 72 h post-infection. These results indicate recruitment of haemocytes upon immersion infection in the gills and degranulation of haemocytes in less infected organs, like the midgut. 相似文献
206.
Pankewitz F Zöllmer A Gräser Y Hilker M 《Archives of insect biochemistry and physiology》2007,66(2):98-108
Eggs of leaf beetles of the tribe Galerucini, subfamily Galerucinae, contain polyketides that are unusual in insects: 1,8-dihydroxylated anthraquinones (chrysazin, chrysophanol) and anthrones (dithranol, chrysarobin) deterring predators. The host plants do not contain these compounds. In the present study, we tested the hypothesis that the beetles, but not bacterial or fungal microorganisms living as endosymbionts within the beetles, produce the anthraquinones. The tansy leaf beetle Galeruca tanaceti was used as Galerucini model organism. It was treated with antimicrobial substances to eradicate the microorganisms and inhibit the hypothesised endosymbiotic anthraquinone production. Despite treatment, female G. tanaceti laid eggs containing anthraquinones. Although broad spectrum antimicrobials were used, it cannot be excluded that the potential endosymbiotic microorganisms are resistant. Given that the hypothesised endosymbionts are transferred via the eggs from one generation to the next, bacterial or fungal DNA was expected to be present in the eggs. With the exception of Wolbachia pipientis, however, no further 16S rDNA from bacteria responsible for anthraquinone biosynthesis was detected in eggs of untreated beetles. Because Wolbachia were also found in closely related anthraquinone-free insects, we exclude these bacteria as producers of the defensive polyketides. Nor was any 18S rDNA from fungi with anthraquinone biosynthetic abilities detected. Our results indicate that anthraquinones and anthrones in eggs of Galerucini are produced by beetle enzymes and not by endosymbiotic microorganisms within the eggs. 相似文献
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210.
Michael Hust Thomas Jostock Christian Menzel Bernd Voedisch Anja Mohr Mariam Brenneis Martina I Kirsch Doris Meier Stefan Dübel 《BMC biotechnology》2007,7(1):14